U.S. patent application number 15/617741 was filed with the patent office on 2017-09-28 for macrocyclic picolinamides as fungicides.
The applicant listed for this patent is DOW AGROSCIENCES LLC. Invention is credited to Karla Bravo-Altamirano, John F. Daeuble, Kyle A. DeKorver, Johnathan E. DeLorbe, Ronald J. Heemstra, Kevin G. Meyer, Chenglin Yao.
Application Number | 20170273303 15/617741 |
Document ID | / |
Family ID | 55064779 |
Filed Date | 2017-09-28 |
United States Patent
Application |
20170273303 |
Kind Code |
A1 |
DeKorver; Kyle A. ; et
al. |
September 28, 2017 |
MACROCYCLIC PICOLINAMIDES AS FUNGICIDES
Abstract
This disclosure relates to macrocyclic picolinamides of Formula
I and their use as fungicides. ##STR00001##
Inventors: |
DeKorver; Kyle A.;
(Lafayette, IN) ; DeLorbe; Johnathan E.;
(Pearland, TX) ; Meyer; Kevin G.; (Zionsville,
IN) ; Yao; Chenglin; (Westfield, IN) ;
Heemstra; Ronald J.; (Fishers, IN) ;
Bravo-Altamirano; Karla; (Carmel, IN) ; Daeuble; John
F.; (Carmel, IN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
DOW AGROSCIENCES LLC |
Indianapolis |
IN |
US |
|
|
Family ID: |
55064779 |
Appl. No.: |
15/617741 |
Filed: |
June 8, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14793315 |
Jul 7, 2015 |
9686984 |
|
|
15617741 |
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62021861 |
Jul 8, 2014 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07D 321/00 20130101;
A01N 43/24 20130101; A01N 43/40 20130101; C07D 405/12 20130101 |
International
Class: |
A01N 43/40 20060101
A01N043/40; C07D 405/12 20060101 C07D405/12; C07D 321/00 20060101
C07D321/00; A01N 43/24 20060101 A01N043/24 |
Claims
1. A compound of Formula I ##STR00151## wherein X is hydrogen or
C(O)R.sub.3; Y is hydrogen, C(O)R.sub.3, or Q; Q is ##STR00152##
R.sub.1 is hydrogen, alkyl, alkenyl, aryl, heterocyclyl, alkoxy, or
acyl, each optionally substituted with 0, 1 or multiple R.sub.6;
R.sub.2 is hydrogen, alkyl, alkenyl, aryl, or acyl, each optionally
substituted with 0, 1 or multiple R.sub.6; R.sub.3 is alkoxy or
benzyloxy, each optionally substituted with 0, 1, or multiple
R.sub.6; R.sub.4 is hydrogen, --C(O)R.sub.5, or
--CH.sub.2OC(O)R.sub.5; R.sub.5 is alkyl, alkoxy, or aryl, each
optionally substituted with 0, 1, or multiple R.sub.6; R.sub.6 is
hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, heteroaryl,
heterocyclyl, or thioalkyl, each optionally substituted with 0, 1,
or multiple R.sub.7; and R.sub.7 is hydrogen, alkyl, aryl, or
halo.
2. The compound according to claim 1, wherein X and Y are
hydrogen.
3. The compound according to claim 2, wherein R.sub.1 is alkyl or
aryl, each optionally substituted with 0, 1 or multiple
R.sub.6.
4. The compound according to claim 2, wherein R.sub.2 is hydrogen
or alkyl, each optionally substituted with 0, 1 or multiple
R.sub.6.
5. The compound according to claim 1, wherein X is C(O)R.sub.3 and
Y is hydrogen.
6. The compound according to claim 5, wherein R.sub.1 is alkyl or
aryl, each optionally substituted with 0, 1 or multiple
R.sub.6.
7. The compound according to claim 5, wherein R.sub.2 is hydrogen
or alkyl, each optionally substituted with 0, 1 or multiple
R.sub.6.
8. The compound according to claim 1, wherein X is hydrogen and Y
is Q.
9. The compound according to claim 8, wherein R.sub.1 is alkyl or
aryl, each optionally substituted with 0, 1 or multiple
R.sub.6.
10. The compound according to claim 8, wherein R.sub.2 is hydrogen
or alkyl, each optionally substituted with 0, 1 or multiple
R.sub.6.
11. The compound according to claim 9, wherein R.sub.4 is
hydrogen.
12. The compound according to claim 9, wherein R.sub.4 is --C(O)R
or --CH.sub.2OC(O)R.sub.5.
13. The compound according to claim 12, wherein R.sub.5 is alkyl or
alkoxy, each optionally substituted with 0, 1, or multiple
R.sub.6.
14. The compound according to claim 13, wherein R.sub.5 is
--CH.sub.3, --CH(CH.sub.3).sub.2, --CH.sub.2OCH.sub.2CH.sub.3, or
--CH.sub.2CH.sub.2OCH.sub.3.
15. A composition for the control of a fungal pathogen including at
least one of the compounds of Formula I and at least one additional
compound selected from the group consisting of: a phytologically
acceptable carrier material, a second fungicide, an insecticide, a
nematocide, a miticide, an arthropodicide, and a bactericide.
16. The composition according to claim 15, wherein the least one
additional compound is at least one phytologically acceptable
carrier material.
17. The composition according to claim 15 wherein the fungal
pathogen is one of Leaf Blotch of Wheat (Mycosphaerella
graminicola; anamorph: Zymoseptoria tritici), Wheat Brown Rust
(Puccinia triticina), Stripe Rust (Puccinia striiformis), Scab of
Apple (Venturia inaequalis), Blister Smut of Maize (Ustilago
maydis), Powdery Mildew of Grapevine (Uncinula necator), Barley
Scald (Rhynchosporium secalis), Blast of Rice (Magnaporthe grisea),
Rust of Soybean (Phakopsora pachyrhizi), Glume Blotch of Wheat
(Leptosphaeria nodorum), Powdery Mildew of Wheat (Blumeria graminis
f. sp. tritici), Powdery Mildew of Barley (Blumeria graminis f. sp.
hordei), Powdery Mildew of Cucurbits (Erysiphe cichoracearum),
Anthracnose of Cucurbits (Glomerella lagenarium), Leaf Spot of Beet
(Cercospora beticola), Early Blight of Tomato (Alternaria solani),
and Net Blotch of Barley (Pyrenophora teres).
18. The composition according to claim 15 wherein the fungal
pathogen is one of Leaf Blotch of Wheat (Zymoseptoria tritici),
Wheat Brown Rust (Puccinia triticina), and Rust of Soybean
(Phakopsora pachyrhizi).
19. A method for the control and/or the prevention of fungal attack
on a plant, the method including the step of: applying a
fungicidally effective amount of at least one of the compounds of
Formula I to at least one portion of a plant, an area adjacent to
the plant, soil adapted to support growth of the plant, a root of
the plant, and at least a portion of foliage of the plant.
20. The method according to claim 19, wherein the method further
includes formulating a composition that includes at least one
additional compound selected from the group consisting of a
phytologically acceptable carrier material, a second fungicide, an
insecticide, a nematocide, a miticide, an arthropodicide, and a
bactericide.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Patent Application Ser. No. 62/021,861 filed Jul. 8, 2014, which is
expressly incorporated by reference herein.
BACKGROUND & SUMMARY
[0002] Fungicides are compounds, of natural or synthetic origin,
which act to protect and/or cure plants against damage caused by
agriculturally relevant fungi. Generally, no single fungicide is
useful in all situations. Consequently, research is ongoing to
produce fungicides that may have better performance, are easier to
use, and cost less.
[0003] The present disclosure relates to macrocyclic picolinamides
and their use as fungicides. The compounds of the present
disclosure may offer protection against ascomycetes,
basidiomycetes, deutcromycetes and oomycctes.
[0004] One embodiment of the present disclosure may include
compounds of Formula I:
##STR00002##
wherein X is hydrogen or C(O)R.sub.3; Y is hydrogen. C(O)R.sub.3,
or Q;
Q is
##STR00003##
[0005] wherein [0006] R.sub.1 is hydrogen, alkyl, alkenyl, aryl,
heterocyclyl, alkoxy, or acyl, each optionally substituted with 0,
1 or multiple R.sub.6; [0007] R.sub.2 is hydrogen, alkyl, alkenyl,
aryl, or acyl, each optionally substituted with 0, 1 or multiple
R.sub.6; [0008] R.sub.3 is alkoxy or benzyloxy, each optionally
substituted with 0, 1, or multiple R.sub.6; [0009] R.sub.4 is
hydrogen, --C(O)R.sub.5, or --CH.sub.2OC(O)R.sub.5; [0010] R.sub.5
is alkyl, alkoxy, or aryl, each optionally substituted with 0, 1,
or multiple R.sub.6; [0011] R.sub.6 is hydrogen, alkyl, aryl, acyl,
halo, alkenyl, alkoxy, heterocyclyl, or thioalkyl, each optionally
substituted with 0, 1, or multiple R.sub.7; [0012] R.sub.7 is
hydrogen, alkyl, aryl, or halo.
[0013] In some embodiments the compound of Formula I includes X
equal to H and Y equal to H; in some of these embodiments R.sub.1
is alkyl or aryl, each optionally substituted with 0, 1 or multiple
R.sub.6; in some of these embodiments R.sub.2 is hydrogen or alkyl,
each optionally substituted with 0, 1 or multiple R.sub.6.
[0014] In some embodiments the compounds of Formula I includes X
equal C(O)R.sub.3 and Y equal to H, in some of these embodiments
R.sub.1 is alkyl or aryl, each optionally substituted with 0, 1 or
multiple R; in some of these embodiments R.sub.2 is hydrogen or
alkyl, each optionally substituted with 0, 1 or multiple
R.sub.6.
[0015] In some embodiments th compounds of Formula I includes X
equal to H and Y equal to Q; in some of these embodiments R.sub.1
is alkyl or aryl, each optionally substituted with 0, 1 or multiple
R.sub.6; in some embodiments R.sub.2 is hydrogen or alkyl, each
optionally substituted with 0, 1 or multiple R.sub.6; in some
embodiments R.sub.4 is either H or --C(O)R.sub.5 or
--CH.sub.2OC(O)R.sub.5; in some of these embodiments R.sub.5 is
alkyl or alkoxy, each optionally substituted with 0, 1, or multiple
R.sub.6, or R.sub.5 is --CH.sub.3, --CH(CH.sub.3).sub.2,
--CH.sub.2OCH.sub.2CH.sub.3, or --CH.sub.2CH.sub.2OCH.sub.3.
[0016] Other embodiments of the present disclosure may include a
fungicidal composition for the control or prevention of fungal
attack comprising the compounds described above and a
phytologically acceptable carrier material.
[0017] Yet other embodiments of the present disclosure may include
a method for the control or prevention of fungal attack on a plant,
the method including the steps of applying a fungicidally effective
amount of one or more of the compounds described above to at least
one of the fungus, the plant, and an area adjacent to the
plant.
[0018] The compounds for Formula I and compostions including the
same as identified herein may be used to control and or prevention
of at least one pathogen such as those selected from the list
consisting of: Leaf Blotch of Wheat (Mycosphaerella graminicola;
anamorph: Zymoseptoria tritici), Wheat Brown Rust (Puccinia
triticina), Stripe Rust (Puccinia striiformis), Scab of Apple
(Venturia inaequalis), Blister Smut of Maize (Ustilago maydis),
Powdery Mildew of Grapevine (Uncinula necator), Barley Scald
(Rhynchosporium secalis), Blast of Rice (Magnaporthe grisea), Rust
of Soybean (Phakopsora pachyrhizi), Glume Blotch of Wheat
(Leptosphaeria nodorum), Powdery Mildew of Wheat (Blumeria graminis
f. sp. tritici), Powdery Mildew of Barley (Blumeria graminis f. sp.
hordei), Powdery Mildew of Cucurbits (Erysiphe cichoracearum),
Anthracnose of Cucurbits (Glomerella lagenarium), Leaf Spot of Beet
(Cercospora beticola), Early Blight of Tomato (Alternaria solani),
and Net Blotch of Barley (Pyrenophora teres).
[0019] Still other embodiments include A method for the control
and/or the prevention of fungal attack on a plant, these methods
including the step of: applying a fungicidally effective amount of
at least one of the compounds of Formula I, or a composition that
includes at least one compound of Formula I to at least one portion
of a plant, an area adjacent to the plant, soil adapted to support
growth of the plant, a root of the plant, and at least a portion of
foliage of the plant. In some embodiments the composition includes
at least one additional compound selected from the group consisting
of a phytologically acceptable carrier material, a second
fungicide, an insecticide, a nematocide, a miticide, an
arthropodicide, and a bactericide.
[0020] It will be understood by those skilled in the art that the
following terms may include generic "R"-groups within their
definitions, e.g., "the term alkoxy refers to an --OR substituent".
It is also understood that within the definitions for the following
terms, these "R" groups are included for illustration purposes and
should not be construed as limiting or being limited by
substitutions about Formula I.
[0021] The term "alkyl" refers to a branched, unbranched, or
saturated cyclic carbon chain, including, but not limited to,
methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl,
pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
and the like.
[0022] The term "alkenyl" refers to a branched, unbranched or
cyclic carbon chain containing one or more double bonds including,
but not limited to, ethenyl, propenyl, butenyl, isopropenyl,
isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the
like.
[0023] The term "alkynyl" refers to a branched or unbranched carbon
chain containing one or more triple bonds including, but not
limited to, propynyl, butynyl, and the like.
[0024] The terms "aryl" and "Ar" refer to any aromatic ring, mono-
or bi-cyclic, containing 0 heteroatom.
[0025] The term "heterocyclyl" refers to any aromatic or
non-aromatic ring, mono- or bi-cyclic, containing one or more
heteroatoms
[0026] The term "alkoxy" refers to an --OR substituent.
[0027] The term "acyloxy" refers to an --OC(O)R substituent.
[0028] The term "cyano" refers to a --C--N substituent.
[0029] The term "hydroxyl" refers to an --OH substituent.
[0030] The term "amino" refers to a --N(R).sub.2 substituent.
[0031] The term "arylalkoxy" refers to --O(CH.sub.2).sub.nAr where
n is an integer selected from the list 1, 2, 3, 4, 5, or 6.
[0032] The term "haloalkoxy" refers to an --OR--X substituent,
wherein X is Cl, F, Br, or I, or any combination thereof.
[0033] The term "haloalkyl" refers to an alkyl, which is
substituted with CI, F, I, or Br or any combination thereof.
[0034] The term "halogen" or "halo" refers to one or more halogen
atoms, defined as F, Cl, Br, and I.
[0035] The term "nitro" refers to a --NO.sub.2 substituent.
[0036] The term thioalkyl refers to an --SR substituent.
[0037] Throughout the disclosure, reference to the compounds of
Formula I is read as also including diastereomers, enantiomers, and
mixtures thereof. In another embodiment. Formula (I) is read as
also including salts or hydrates thereof. Exemplary salts include,
but are not limited to: hydrochloride, hydrobromide, and
hydroiodide.
[0038] It is also understood by those skilled in the art that
additional substitution is allowable, unless otherwise noted, as
long as the rules of chemical bonding and strain energy are
satisfied and the product still exhibits fungicidal activity.
[0039] Another embodiment of the present disclosure is a use of a
compound of Formula I, for protection of a plant against attack by
a phytopathogenic organism or the treatment of a plant infested by
a phytopathogenic organism, comprising the application of a
compound of Formula I, or a composition comprising the compound to
soil, a plant, a part of a plant, foliage, and/or roots.
[0040] Additionally, another embodiment of the present disclosure
is a composition useful for protecting a plant against attack by a
phytopathogenic organism and/or treatment of a plant infested by a
phytopathogenic organism comprising a compound of Formula I and a
phytologically acceptable carrier material.
DETAILED DESCRIPTION
[0041] The compounds of the present disclosure may be applied by
any of a variety of known techniques, either as the compounds or as
formulations comprising the compounds. For example, the compounds
may be applied to the roots or foliage of plants for the control of
various fungi, without damaging the commercial value of the plants.
The materials may be applied in the form of any of the generally
used formulation types, for example, as solutions, dusts, wettable
powders, flowable concentrate, or emulsifiable concentrates.
[0042] Preferably, the compounds of the present disclosure are
applied in the form of a formulation, comprising one or more of the
compounds of Formula I with a phytologically acceptable carrier.
Concentrated formulations may be dispersed in water, or other
liquids, for application, or formulations may be dust-like or
granular, which may then be applied without further treatment. The
formulations can be prepared according to procedures that are
conventional in the agricultural chemical art.
[0043] The present disclosure contemplates all vehicles by which
one or more of the compounds may be formulated for delivery and use
as a fungicide. Typically, formulations are applied as aqueous
suspensions or emulsions. Such suspensions or emulsions may be
produced from water-soluble, water-suspendible, or emulsifiable
formulations which are solids, usually known as wettable powders;
or liquids, usually known as emulsifiable concentrates, aqueous
suspensions, or suspension concentrates. As will be readily
appreciated, any material to which these compounds may be added may
be used, provided it yields the desired utility without significant
interference with the activity of these compounds as antifungal
agents.
[0044] Wettable powders, which may be compacted to form
water-dispersible granules comprise an intimate mixture of one or
more of the compounds of Formula I, an inert carrier and
surfactants. The concentration of the compound in the wettable
powder may be from about 10 percent to about 90 percent by weight
based on the total weight of the wettable powder, more preferably
about 25 weight percent to about 75 weight percent. In the
preparation of wettable powder formulations, the compounds may be
compounded with any finely divided solid, such as prophyllite,
talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite,
starch, casein, gluten, montmorillonite clays, diatomaceous earths,
purified silicates or the like. In such operations, the finely
divided carrier and surfactants are typically blended with the
compound(s) and milled.
[0045] Emulsifiable concentrates of the compounds of Formula I may
comprise a convenient concentration, such as from about 1 weight
percent to about 50 weight percent of the compound, in a suitable
liquid, based on the total weight of the concentrate. The compounds
may be dissolved in an inert carrier, which is either a
water-miscible solvent or a mixture of water-immiscible organic
solvents, and emulsifiers. The concentrates may be diluted with
water and oil to form spray mixtures in the form of oil-in-water
emulsions. Useful organic solvents include aromatics, especially
the high-boiling naphthalenic and olefinic portions of petroleum
such as heavy aromatic naphtha. Other organic solvents may also be
used, for example, terpenic solvents, including rosin derivatives,
aliphatic ketones, such as cyclohexanone, and complex alcohols,
such as 2-ethoxyethanol.
[0046] Emulsifiers which may be advantageously employed herein may
be readily determined by those skilled in the art and include
various nonionic, anionic, cationic and amphoteric emulsifiers, or
a blend of two or more emulsifiers. Examples of nonionic
emulsifiers useful in preparing the emulsifiable concentrates
include the polyalkylene glycol ethers and condensation products of
alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or
fatty acids with ethylene oxide, propylene oxides such as the
ethoxylated alkyl phenols and carboxylic esters solubilized with
the polyol or polyoxyalkylene. Cationic emulsifiers include
quaternary ammonium compounds and fatty amine salts. Anionic
emulsifiers include the oil-soluble salts (e.g., calcium) of
alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol
ethers and appropriate salts of phosphated polyglycol ether.
[0047] Representative organic liquids which may be employed in
preparing the emulsifiable concentrates of the compounds of the
present disclosure are the aromatic liquids such as xylene, propyl
benzene fractions; or mixed naphthalene fractions, mineral oils,
substituted aromatic organic liquids such as dioctyl phthalate;
kerosene; dialkyl amides of various fatty acids, particularly the
dimethyl amides of fatty glycols and glycol derivatives such as the
n-butyl ether, ethyl ether or methyl ether of diethylene glycol,
the methyl ether of triethylene glycol, petroleum fractions or
hydrocarbons such as mineral oil, aromatic solvents, paraffinic
oils, and the like; vegetable oils such as soy bean oil, rape seed
oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn
oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower
oil, sesame oil, tung oil and the like; esters of the above
vegetable oils; and the like. Mixtures of two or more organic
liquids may also be employed in the preparation of the emulsifiable
concentrate. Organic liquids include xylene, and propyl benzene
fractions, with xylene being most preferred in some cases.
Surface-active dispersing agents are typically employed in liquid
formulations and in an amount of from 0.1 to 20 percent by weight
based on the combined weight of the dispersing agent with one or
more of the compounds. The formulations can also contain other
compatible additives, for example, plant growth regulators and
other biologically active compounds used in agriculture.
[0048] Aqueous suspensions comprise suspensions of one or more
water-insoluble compounds of Formula I, dispersed in an aqueous
vehicle at a concentration in the range from about 1 to about 50
weight percent, based on the total weight of the aqueous
suspension. Suspensions are prepared by finely grinding one or more
of the compounds, and vigorously mixing the ground material into a
vehicle comprised of water and surfactants chosen from the same
types discussed above. Other components, such as inorganic salts
and synthetic or natural gums, may also be added to increase the
density and viscosity of the aqueous vehicle.
[0049] The compounds of Formula I can also be applied as granular
formulations, which are particularly useful for applications to the
soil. Granular formulations generally contain from about 0.5 to
about 10 weight percent, based on the total weight of the granular
formulation of the compound(s), dispersed in an inert carrier which
consists entirely or in large part of coarsely divided inert
material such as attapulgite, bentonite, diatomite, clay or a
similar inexpensive substance. Such formulations are usually
prepared by dissolving the compounds in a suitable solvent and
applying it to a granular carrier which has been preformed to the
appropriate particle size, in the range of from about 0.5 to about
3 mm. A suitable solvent is a solvent in which the compound is
substantially or completely soluble. Such formulations may also be
prepared by making a dough or paste of the carrier and the compound
and solvent, and crushing and drying to obtain the desired granular
particle.
[0050] Dusts containing the compounds of Formula I may be prepared
by intimately mixing one or more of the compounds in powdered form
with a suitable dusty agricultural carrier, such as, for example,
kaolin clay, ground volcanic rock, and the like. Dusts can suitably
contain from about 1 to about 10 weight percent of the compounds,
based on the total weight of the dust.
[0051] The formulations may additionally contain adjuvant
surfactants to enhance deposition, wetting, and penetration of the
compounds onto the target crop and organism. These adjuvant
surfactants may optionally be employed as a component of the
formulation or as a tank mix. The amount of adjuvant surfactant
will typically vary from 0.01 to 1.0 percent by volume, based on a
spray-volume of water, preferably 0.05 to 0.5 volume percent.
Suitable adjuvant surfactants include, but are not limited to
ethoxylated nonyl phenols, ethoxylated synthetic or natural
alcohols, salts of the esters or sulphosuccinic acids, ethoxylated
organosilicones, ethoxylated fatty amines, blends of surfactants
with mineral or vegetable oils, crop oil concentrate (mineral oil
(85%)+emulsifiers (15%)); nonylphenol ethoxylate;
benzylcocoalkyldimethyl quaternary ammonium salt; blend of
petroleum hydrocarbon, alkyl esters, organic acid, and anionic
surfactant; C.sub.9-C.sub.11 alkylpolyglycoside; phosphated alcohol
ethoxylate; natural primary alcohol (C.sub.2-C.sub.16) ethoxylate;
di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap;
nonylphenol ethoxylate+urea ammonium nitrate; emulsified methylated
seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow
amine ethoxylate (15 EO); PEG(400) dioleate-99. The formulations
may also include oil-in-water emulsions such as those disclosed in
U.S. patent application Ser. No. 11/495,228, the disclosure of
which is expressly incorporated by reference herein.
[0052] The formulations may optionally include combinations that
contain other pesticidal compounds. Such additional pesticidal
compounds may be fungicides, insecticides, herbicides, nematocides,
miticides, arthropodicides, bactericides or combinations thereof
that are compatible with the compounds of the present disclosure in
the medium selected for application, and not antagonistic to the
activity of the present compounds. Accordingly, in such
embodiments, the other pesticidal compound is employed as a
supplemental toxicant for the same or for a different pesticidal
use. The compounds of Formula I and the pesticidal compound in the
combination can generally be present in a weight ratio of from
1:100 to 100:1.
[0053] The compounds of the present disclosure may also be combined
with other fungicides to form fungicidal mixtures and synergistic
mixtures thereof. The fungicidal compounds of the present
disclosure are often applied in conjunction with one or more other
fungicides to control a wider variety of undesirable diseases. When
used in conjunction with other fungicide(s), the presently claimed
compounds may be formulated with the other fungicide(s), tank-mixed
with the other fungicide(s) or applied sequentially with the other
fungicide(s). Such other fungicides may include
2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol,
8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin,
Ampelomyces quisqualis, azaconazole, azoxystrobin, Bacillus
subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl,
benthiavalicarb-isopropyl, benzovindiflupyr
benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl,
bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux
mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide,
captafol, captan, carbendazim, carboxin, carpropamid, carvone,
chlazafenone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium
minitans, copper hydroxide, copper octanoate, copper oxychloride,
copper sulfate, copper sulfate (tribasic), cuprous oxide,
cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil,
dazomet, debacarb, diammonium ethylenebis-(dithiocarbamate),
dichlofluanid, dichlorophen, diclocymet, diclomezine, dichloran,
diethofencarb, difenoconazole, difenzoquat ion, diflumetorim,
dimethomorph, dimoxystrobin, diniconazole, diniconazole-M,
dinobuton, dinocap, diphenylamine, dithianon, dodemorph, dodemorph
acetate, dodine, dodine free base, edifenphos, enestrobin,
enestroburin, epoxiconazole, ethiaboxam, ethoxyquin, etridiazole,
famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram,
fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph,
fenpyrazamine, fentin, fentin acetate, fentin hydroxide, ferbam,
ferimozone, fluazinam, fludioxonil, flumorph, fluopicolide,
fluopyram, fluoroimide, fluoxastrobin, fluquinconazole,
flusilazole, flusulfamide, flutianil, flutolanil, flutriafol,
fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminium,
fluberidazole, furalaxyl, furametpyr, guazatine, guazatine
acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol,
imazalil, imazalil sulfate, imibenconazole, iminoctadine,
iminoctadine triacetate, iminoctadine tris(albesilate), iodocarb,
ipconazole, ipfenpyrazolone, iprobenfos, iprodione, iprovalicarb,
isoprothiolane, isopyrazam, isotianil, kasugamycin, kasugamycin
hydrochloride hydrate, kresoxim-methyl, laminarin, mancopper,
mancozeb, mandipropamid, maneb, mefenoxam, mepanipyrim, mepronil,
meptyl-dinocap, mercuric chloride, mercuric oxide, mercurous
chloride, metalaxyl, metalaxyl-M, metam, metam-ammonium,
metam-potassium, metam-sodium, metconazole, methasulfocarb, methyl
iodide, methyl isothiocyanate, metiram, metominostrobin,
metrafenone, mildiomycin, myclobutanil, nabam, nitrothal-isopropyl,
nuarimol, octhilinone, ofurace, oleic acid (fatty acids),
orysastrobin, oxadixyl, oxine-copper, oxpoconazole fumarate,
oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen,
petachlorophenol, pentachlorophenyl laurate, penthiopyrad,
phenylmercury acetate, phosphonic acid, phthalide, picoxystrobin,
polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassium
hydroxyquinoline sulfate, probenazole, prochloraz, procymidone,
propamocarb, propamocarb hydrochloride, propiconazole, propineb,
proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin,
pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox,
pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen,
quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam,
simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodium
pentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, tar oils,
tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole,
thifluzamide, thiophanate-methyl, thiram, tiadinil,
tolclofos-methyl, tolylfluanid, triadimefon, triadimenol,
triazoxide, tricyclazole, tridemorph, trifloxystrobin,
triflumizole, triforine, triticonazole, validamycin, valifenalate,
valiphenal, vinclozolin, zineb, ziram, zoxamide, Candida oleophila,
Fusarium oxysporum, Gliocladium spp., Phlebiopsis gigantea,
Strepomyces griseoviridis, Trichoderma spp.,
(RS)-N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide,
1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone
hydrate, 1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane,
2-(2-heptadecyl-2-imidazolin-1-yl)ethanol,
2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide,
2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride,
2-methoxyethylmercury silicate,
3-(4-chlorophenyl)-5-methylrhodanine, 4-(2-nitroprop-1-enyl)phenyl
thiocyanateme, ampropylfos, anilazine, azithiram, barium
polysulfide, Bayer 32394, benodanil, benquinox, bentaluron,
benzamacril; benzamacril-isobutyl, benzamorf, binapacryl,
bis(methylmercury) sulfate, bis(tributyltin) oxide, butiobate,
cadmium calcium capper zinc chromate sulfate, carbamorph, CECA,
chlobenthiazone, chloraniformethan, chlorfenazole, chlorquinox,
climbazole, copper bis(3-phenylsalicylate), copper zinc chromate,
cufraneb, cupric hydrazinium sulfate, cuprobam, cyclafuramid,
cypendazole, cyprofuram, decafentin, dichlone, dichlozoline,
diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon,
dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, ESBP,
etaconazole, etem, ethirim, fenaminosulf, fenapanil, fenitropan,
fluotrimazole, furcarbanil, furconazole, furconazole-cis,
furmecyclox, furophanate, glyodine, griseoflulvin, halacrinate,
Hercules 3944, hexylthiofos, ICIA085, isopamphos, isovaledione,
mebenil, mecarbinzid, metazoxolon, methfuroxam, methylmercury
dicyandiamide, metsulfovax, milneb, mucochloric anhydride,
myclozolin, N-3,5-dichlorophenyl-succinimide,
N-3-nitrophenylitaconimide, natamycin,
N-ethylmercurio-4-toluenesulfonanilide, nickel
bis(dimethyldithiocarbamate), OCH, phenylmercury
dimethyldithiocarbamate, phenylmercury nitrate, phosdiphen,
prothiocarb; prothiocarb hydrochloride, pyracarbolid, pyridinitril,
pyroxychlor, pyroxyfur, quinacetol; quinacetol sulfate, quinazamid,
quinconazole, rabenzazole, salicylanilide, SSF-109, sultropen,
tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate,
thioquinox, tioxymid, triamiphos, triarimol, triazbutil,
trichlamide, urbacid, zarilamid, and any combinations thereof.
[0054] Additionally, the compounds described herein may be combined
with other pesticides, including insecticides, nematocides,
miticides, arthmpodicides, bactericides or combinations thereof
that are compatible with the compounds of the present disclosure in
the medium selected for application, and not antagonistic to the
activity of the present compounds to form pesticidal mixtures and
synergistic mixtures thereof. The fungicidal compounds of the
present disclosure may be applied in conjunction with one or more
other pesticides to control a wider variety of undesirable pests.
When used in conjunction with other pesticides, the presently
claimed compounds may be formulated with the other pesticide(s),
tank-mixed with the other pesticide(s) or applied sequentially with
the other pesticide(s). Typical insecticides include, but are not
limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid,
acethion, acetoprole, acrinathrin, acrylonitrile, alanycarb,
aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb,
alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion,
aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion,
azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl,
azothoate, barium hexafluorosilicate, barthrin, bendiocarb,
benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin,
bifenthrin, bioallethrin, bioethanomethrin, biopermethrin,
bistrifluron, borax, boric acid, bromfenvinfos, bromocyclen,
bromo-DDT, bromophos, bromophos-ethyl, bufencarb, buprofezin,
butacarb, butathiofos, butocarboxim, butonate, butoxycarboxim,
cadusafos, calcium arsenate, calcium polysulfide, camphechlor,
carbanolate, carbaryl, carbofuran, carbon disulfide, carbon
tetrachloride, carbophenothion, carbosulfan, cartap, cartap
hydrochloride, chlorantraniliprole, chlorbicyclen, chlordane,
chlordecone, chlordimeform, chlordimeform hydrochloride,
chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron,
chlormephos, chloroform, chloropicrin, chlorphoxim, chlorprazophos,
chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide,
cinerin I, cinerin II, cinerins, cismethrin, cloethocarb,
closantel, clothianidin, capper acetoarsenite, copper arsenate,
copper naphthenate, copper oleate, coumaphos, coumithoate,
crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos,
cyanophos, cyanthoate, cyantraniliprole, cyclethrin, cycloprothrin,
cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, cymomazine,
cythioate, DDT, decarbofuran, deltamethrin, demephion, demephion-O,
demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl,
demeton-S, demeton-S-methyl, demeton-S-methylsulphon,
diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon,
dichlofenthion, dichlorvos, dicresyl, dicrotophos, dicyclanil,
dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan,
dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex,
dinex-diclexine, dinoprop, dinosam, dinotefuran, diofenolan,
dioxabenzofos, dioxacarb, dioxathion, disulfoton, dithierofos,
d-limonene, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium,
doramectin, ecdysterone, emamectin, emamectin benzoate, EMPC,
empenthrin, endosulfan, endothion, endrin, EPN, epofenonane,
eprinomectin, esdepallethrine, esfenvalerate, etaphos,
ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl
formate, ethyl-DDD, ethylene dibromide, ethylene dichloride,
ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos,
fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion,
fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin,
fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil,
flonicamid, flubendiamide, flucofuron, flucycloxuron,
flucythrinate, flufenerim, flufenoxuron, flufenprox, fluvalinate,
fonofos, formetanate, formetanate hydrochloride, formothion,
formparanate, formparanate hydrochloride, fosmethilan, fospirate,
fosthietan, furathiocarb, furethrin, gamma cyhalothrin, gamma-HCH,
halfenprox, halofenozide, HCH, HEOD, heptachlor, heptenophos,
heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide,
hydroprene, hyquincarb, imidacloprid, imiprothrin, indoxacarb,
iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isodrin,
isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane,
isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II,
jodfenphos, juvenile hormone I, juvenile hormone II, juvenile
hormone III, kelevan, kinoprene, lambda-cyhalothrin, lead arsenate,
lepimectin, leptophos, lindane, lirimfos, lufenuron, lythidathion,
malathion, malonoben, mazidox, mecarbam, mecarphon, menazon,
mephosfolan, mercurous chloride, mesulfenfos, metaflumizone,
methacrifos, methamidophos, methidathion, methiocarb,
methocrotophos, methomyl, methoprene, methoxychlor,
methoxyfenozide, methyl bromide, methyl isothiocyanate,
methylchloroform, methylene chloride, metofluthrin, metolcarb,
metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin
oxime, mipafox, mirex, molosultap, monocrotophos, monomehypo,
monosultap, morphothion, moxidectin, naftalofos, naled,
naphthalene, nicotine, nifluridide, nitenpyram, nithiazine,
nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl,
oxydemeton-methyl, oxydeprofos, oxydisulfoton,
para-dichlorabenzene, parathion, parathion-methyl, penfluron,
pentachlorophenol, permethrin, phenkapton, phenothrin, phenthoate,
phorate, phosalone, phosfolan, phosmet, phosnichlor, phosphamidon,
phosphine, phoxim, phoxim-methyl, pirimetaphos, pirimicarb,
pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium
thiocyanate, pp'-DDT, prallethrin, precocene I, precocene II,
precocene III, primidophos, profenofos, profluralin, promacyl,
promecarb, propaphos, propetamphos, propoxur, prothidathion,
prothiofos, prothoate, protrifenbute, pyraclofos, pyrafluprole,
pyrazophos, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins,
pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon,
pyrimidifen, pyrimitate, pyriprole, pyriproxyfen, quassia,
quinalphos, quinalphos-methyl, quinothion, rafoxanide, resmethrin,
rotenone, ryania, sabadilla, schradan, selamectin, silafluofen,
silica gel, sodium arsenite, sodium fluoride, sodium
hexafluorosilicate, sodium thiocyanate, sophamide, spinetoram,
spinosad, spiromesifen, spirotetramat, sulcofuron,
sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfuryl
fluoride, sulprofos, tau-fluvalinate, tazimearb, TDE, tebufenozide,
tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos,
TEPP, terallethrin, terbufos, tetrachloroethane, tetrachlorvinphos,
tetramethrin, tetramethylfluthrin, theta-cypermethrin, thiacloprid,
thiamethoxam, thierofos, thiocarboxime, thiocyclam, thiocyclam
oxalate, thiodicarb, thiofanox, thiometon, thiosultap,
thiosultap-disodium, thiosultap-monosodium, thuringiensin,
tolfenpyrad, tralomethrin, transfluthrin, transpermethrin,
triarathene, triazamate, triazophos, trichlorfon,
trichlormetaphos-3, trichloronat, trifenofos, triflumuron,
trimethacarb, triprene, vamidothion, vanziliprole, XMC, xylylcarb,
zeta-cypermethrin, zolaprofos, and any combinations thereof.
[0055] Additionally, the compounds described herein may be combined
with herbicides that are compatible with the compounds of the
present disclosure in the medium selected for application, and not
antagonistic to the activity of the present compounds to form
pesticidal mixtures and synergistic mixtures thereof. The
fungicidal compounds of the present disclosure may be applied in
conjunction with one or more herbicides to control a wide variety
of undesirable plants. When used in conjunction with herbicides,
the presently claimed compounds may be formulated with the
herbicide(s), tank-mixed with the herbicide(s) or applied
sequentially with the herbicide(s). Typical herbicides include, but
are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB;
3,4-DB; 2,4-DEB: 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB;
acetochlor, acifluorfen, aclonifen, acrolein, alachlor,
allidochlor, alloxydim, allyl alcohol, alorac, ametridione,
ametryn, amibuzin, amicarbazone, amidosulfuron,
aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole,
ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine,
azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid,
benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron,
bensulide, bentazone, benzadox, benzfendizone, benzipram,
benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron,
bicyclopyrone, bifenox, bilanafos, bispyribac, borax, bromacil,
bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon,
butachlor, butafenacil, butamifos, butenachlor, buthidazole,
buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid,
cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor,
carbasulam, carbetamide, carboxazole chlorprocarb, carfentrazone,
CDEA, CEPC, chlomethoxyfen, chloramben, chloranocryl, chlorazifop,
chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac,
chlorfenprop, chlorflurazole, chlorflurenol, chloridazon,
chlorimuron, chlornitrofen, chloropon, chlorotoluron, chloroxuron,
chloroxynil, chlorpropham, chlorsulfuron, chlorthal, chlorthiamid,
cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clethodim,
cliodinate, clodinafop, clofop, clomazone, clomeprop, cloprop,
cloproxydim, clopyralid, cloransulam, CMA, copper sulfate, CPMF,
CPPC, crdazine, cresol, cumyluron, cyanatryn, cyanazine, cycloate,
cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyperquat,
cyprazine, cyprazole, cypromid, daimuron, dalapon, dazomet,
delachlor, desmedipham, desmetryn, di-allate, dicamba, dichlobenil,
dichloralurea, dichlormate, dichlorprop, dichlorprop-P, diclofop,
diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron,
difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepipcrate,
dimethachlor, dimethametryn, dimethenamid, dimethenamid-P,
dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam,
dinoseb, dinoterb, diphenamid, dipropetryn, diquat, disul,
dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal,
epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethazmetsulfuron,
ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxysulfiuron,
etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop,
fenoxaprop, fenoxaprop-P, fenoxasulfone, fenteracol, fenthiaprop,
fentrazamide, fenuron, ferrous sulfate, flamprop, flamprop-M,
flazasulfuron, florasulam, fluazifop, fluazifop-P, fluazolate,
flucarbazone, flucetosulfuron, fluchloralin, flufenacet,
flufenican, flufenpyr, flumetsulam, flumezin, flumiclorac,
flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen,
fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil,
flupropanate, flupyrsulfuron, fluridone, flurochloridone,
fluroxypyr, flurtamone, fluthiacet, fomesafen, foramsulfuron,
fosamine, furyloxyfen, glufosinate, glufosinate-P, glyphosate,
halauxifen, halosafen, halosulfuron, haloxydine, haloxyfop,
haloxyfop-P, hexachloroacetone, hexaflurate, hexazinone,
imazamethabenz, imazamox, imazapic, imazapyr, imazaquin,
imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil,
iodomethane, iodosulfuron, ioxynil, ipazine, ipfencarbazone,
iprymidam, isocarbamid, isocil, isomethiozin, isonoruron,
isopolinate, isopropalin, isoproturon, isouron, isoxaben,
isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate,
ketospiradox, lactofen, lenacil, linuron, MAA, MAMA, MCPA,
MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, mefenacet,
mefluidide, mesoprazine, mesosulfuron, mesotrione, metamn,
metamifop, metamitron, metazachlor, metazosulfuron, metflurazon,
methabenzthiaxuron, methalpropalin, methazole, methiobencarb,
methiozolin, methiuron, methometon, methoprotryne, methyl bromide,
methyl isothiocyanate, methyldymron, metobenzuron, metobromuron,
mectolachlor, metosulam, metoxuron, metribuzin, metsulfuron,
molinate, monalide, monisouron, monochloroacetic acid, monolinuron,
monuron, morfamquat, MSMA, naproanilide, napropamide, naptalam,
neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen,
nitrofluorfen, norflurazon, noruron, OCH, orbencarb,
ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl,
oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen,
parafluron, paraquat, pebulate, pelargonic acid, pendimethalin,
penoxsulam, pentachlorophenol, pentanochlor, pentoxazone,
perfluidone, pethoxamid, phenisopham, phenmedipham,
phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram,
picolinafen, pinoxaden, piperophos, potassium arsenite, potassium
azide, potassium cyanate, pretilachlor, primisulfuron, procyazine,
prodiamine, profluazol, profluralin, profoxydim, proglinazine,
prometon, prometryn, propachlor, propanil, propaquizafop,
propazine, propham, propisochlor, propoxycarbazone,
propyrisulfuron, propyzamide, prosulfalin, prosulfocarb,
prosulfuron, proxan, prynachlor, pydanon, pyraclonil, pyraflufen,
pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazoxyfen,
pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate,
pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac, pyroxasulfone,
pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid,
quizalofop, quizalofop-P, rhodethanil, rimsulfuron, saflufenacil,
S-metolachlor, sebuthylazine, secbumeton, sethoxydim, siduron,
simazine, simeton, simetryn, SMA, sodium arsenite, sodium azide,
sodium chlorate, sulcotrione, sulfallate, sulfentrazone,
sulfometuron, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA,
tebutam, tebuthiuron, tefuryltrion, tembotrione, tepraloxydim,
terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine,
terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr,
thidiazimin, thidiazuron, thiencarbazone-methyl, thifensulfuron,
thiobencarb, tiocarbazil, tioclorim, topramezone, tralkoxydim,
triafamone, tri-allate, triasulfuron, triaziflam, tribenuron,
tricamba, triclopyr, tridiphane, trietazine, trifloxysulfuron,
trifluralin, triflusulfuron, trifop, trifopsime,
trihydroxytriazine, trimeturon, tripropindan, tritac,
tritosutfuron, vernolate, and xylachlor.
[0056] Another embodiment of the present disclosure is a method for
the control or prevention of fungal attack. This method comprises
applying to the soil, plant, roots, foliage, or locus of the
fungus, or to a locus in which the infestation is to be prevented
(for example applying to cereal or grape plants), a fungicidally
effective amount of one or more of the compounds of Formula I. The
compounds are suitable for treatment of various plants at
fungicidal levels, while exhibiting low phytotoxicity. The
compounds may be useful both in a protectant and/or an eradicant
fashion.
[0057] The compounds have been found to have significant fungicidal
effect particularly for agricultural use. Many of the compounds are
particularly effective for use with agricultural crops and
horticultural plants.
[0058] It will be understood by those skilled in the art that the
efficacy of the compound for the foregoing fungi establishes the
general utility of the compounds as fungicides.
[0059] The compounds have broad ranges of activity against fungal
pathogens. Exemplary pathogens may include, but are not limited to,
causing agent of wheat leaf blotch (Mycosphaerella graminicola;
anamorph: Septoria tritici), wheat brown rust (Puccinia triticina,
wheat stripe rust (Puccinia striiformis), scab of apple (Venturia
inaequalis), powdery mildew of grapevine (Uncinula necator), barley
scald (Rhynchosporium secalis), blast of rice (Magnaporthe grisea),
rust of soybean (Phakopsora packyrhizi), glume blotch of wheat
(Leptosphaeria nodorum), powdery mildew of wheat (Blumeria graminis
f. sp. tritici), powdery mildew of barley (Blumeria graminis f. sp.
hordei), powdery mildew of cucurbits (Erysiphe cichoracearum),
anthracnose of cucurbits (Glomerella lagenarium), leaf spot of beet
(Cercospora beticola), early blight of tomato (Alternaria solani),
and spot blotch of barley (Cochliobolus sativus). The exact amount
of the active material to be applied is dependent not only on the
specific active material being applied, but also on the particular
action desired, the fungal species to be controlled, and the stage
of growth thereof, as well as the part of the plant or other
product to be contacted with the compound. Thus, all the compounds,
and formulations containing the same, may not be equally effective
at similar concentrations or against the same fungal species.
[0060] The compounds are effective in use with plants in a
disease-inhibiting and phytologically acceptable amount. The term
"disease-inhibiting and phytologically acceptable amount" refers to
an amount of a compound that kills or inhibits the plant disease
for which control is desired, but is not significantly toxic to the
plant. This amount will generally be from about 0.1 to about 1000
ppm (parts per million), with 1 to 500 ppm being preferred. The
exact concentration of compound required varies with the fungal
disease to be controlled, the type of formulation employed, the
method of application, the particular plant species, climate
conditions, and the like. A suitable application rate is typically
in the range from about 0.10 to about 4 pounds/acre (about 0.01 to
0.45 grams per square meter, g/m.sup.2).
[0061] Any range or desired value given herein may be extended or
altered without losing the effects sought, as is apparent to the
skilled person for an understanding of the teachings herein.
[0062] The compounds of Formula I may be made using well-known
chemical procedures. Intermediates not specifically mentioned in
this disclosure are either commercially available, may be made by
routes disclosed in the chemical literature, or may be readily
synthesized from commercial starting materials utilizing standard
procedures.
GENERAL SCHEMES
[0063] The following schemes illustrate approaches to generating
picolinamide compounds of Formula (I). The following descriptions
and examples are provided for illustrative purposes and should not
be construed as limiting in terms of substituents or substitution
patterns.
[0064] Compounds of Formula 1.3, where R.sub.1 is as originally
defined, can be prepared according to the methods outlined in
Scheme 1, steps a-c. Compounds of Formula 1.1, where R.sub.1 is as
originally defined, can be obtained by reaction of the dianion of
an ester of Formula 1.0 formed by treatment with lithium
diisopropyl amide (LDA) at -50.degree. C., with an alkyl halide or
allyl halide in a solvent such as tetrahydrofuran (THF) at
cryogenic temperatures such as -78.degree. C., as shown in a.
Compounds of Formula 1.2, where R.sub.1 is as originally defined,
can be obtained by treating compounds of Formula 1.1, where R.sub.1
is an alkenyl functionality, with hydrogen gas (HA) in the presence
of a catalyst such as palladium on carbon (Pd/C) in a solvent such
as ethyl acetate (EtOAc) or methanol (MeOH), as shown in b.
Compounds of Formula 1.3, where R.sub.1 is as originally defined,
can be prepared from compounds of Formula 1.1, where R.sub.1 is as
defined above, and Formula 1.2, where R.sub.1 is as defined above,
by treating with an alkylating agent such as 4-methoxybenzyl
2,2,2-trichloroacetimidate in the presence of an acid such as ((1
S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonic
acid (camphor sulfonic acid, CSA) in a solvent such as
dichloromethane (DCM), as depicted in c.
##STR00004##
[0065] Compounds of Formulas 2.3 and 2.4, where R.sub.1 and R.sub.2
are as originally defined can be prepared as shown in Scheme 2,
steps a-e. Aldehydes of Formula 2.0, where R.sub.1 is as originally
defined, can be obtained by the reduction of esters of Formula 1.3,
where R.sub.1 is as defined above, using a catalyst such as
chlorobis(cyclooctene)iridium(I) dimer in the presence of a
reducing agent such as diethylsilane (Et.sub.2SiH.sub.2) in a
solvent such as DCM, as shown in a. Alcohols of Formula 2.1, where
R.sub.1 and R.sub.2 are as originally defined, can be obtained by
treatment of aldehydes of Formula 2.0, where R.sub.1 is as defined
above, with a nucleophile, such as benzyl magnesium chloride, vinyl
magnesium bromide, and allyl magnesium bromide, in a solvent such
as THF at a temperature of about 0.degree. C. or -78.degree. C. as
shown in b. Alcohols of Formula 2.1, with R.sub.1 and R.sub.2 as
defined above can be oxidized with an oxidizing agent such as
Dess-Martin periodinane (DMP) in a solvent such as DCM to afford
compounds of Formula 2.2, where R.sub.1 and R.sub.2 are as
originally defined as shown in c. Alcohols of Formula 2.3, where
R.sub.1 and R.sub.2 are as previously defined, can be prepared from
ketones of Formula 2.2, where R.sub.1 and R.sub.2 are as defined
above, by treatment with a reducing agent such as borane dimethyl
sulfide (BH.sub.3-DMS) in the presence of a chiral catalyst such as
(S)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole
in a solvent such as toluene as depicted in d. Alcohols of 2.4,
where R.sub.1 is as previously defined, can be prepared as shown in
e from esters of Formula 1.3, where R.sub.1 is as originally
defined, by treatment with a reducing agent such as lithium
aluminum hydride (LAH) in a solvent such as THF at a temperature
between about 0.degree. C. and 23.degree. C.
##STR00005##
[0066] Compounds of Formula 3.2, where R.sub.1 and R.sub.2 are as
originally defined, but R.sub.2 is not alkenyl, can be prepared
according to the methods outlined in Scheme 3, steps a-c. Alcohol
of Formula 2.3, where R.sub.1 and R.sub.2 are as originally
defined, but R.sub.2 is not alkenyl, can be treated with a base
such as sodium hydride (NaH) and an allylic halide such as allyl
bromide in a polar, aprotic solvent such as THF or
N,N-dimethylformamide (DMF) to afford compounds of Formula 3.0,
where R.sub.1 and R.sub.2 are as originally defined, as shown in a.
Compounds of Formula 3.1, where R.sub.1 and R.sub.2 are as
originally defined, but R.sub.2 is not alkenyl, can be prepared
from compounds of Formula 3.0, where R.sub.1 and R.sub.2 are as
previously defined, by treating with ozone in a solvent mixture
such as DCM and MeOH, followed by quenching with a reducing agent
such as triphenylphosphine (PPh.sub.3) as shown in b. Compounds of
Formula 3.1, where R.sub.1 and R.sub.2 are as defined above, can be
treated with an ylide precursor such as methyl
2-((tert-butoxycarbonyl)amino)-2-(dimethoxyphosphoryl)acetate and a
base such as 1.8-diazabicyclo[5.4.0]undec-7-ene (DBU) in a
halogenated solvent such as DCM to afford compounds of Formula 3.2,
where R.sub.1 and R.sub.2 are as previously defined, as shown in
c.
##STR00006##
[0067] Compounds of Formula 4.1.4.4 and 4.5, where R.sub.1 and
R.sub.6 are as originally defined, can be prepared according to the
methods outlined in Scheme 4, steps a-e. Alcohols of Formula 2.3,
where R.sub.1 is as originally defined, can be treated with abase
such as NaH and a reagent such as 2-bromo-1,1-diethoxyethane in a
solvent such as DMF, acetonitrile (CH.sub.3CN), or mixtures thereof
at a temperature of about 50.degree. C. to afford compounds of
Formula 4.0, where R.sub.1 is as originally defined, as depicted in
a. Compounds of Formula 4.1, where R.sub.1 and R.sub.6 are as
originally defined can be prepared as shown in b from compounds of
Formula 4.0, where R.sub.1 is as previously defined, by first
treating with 9-borabicyclo[3.3.1]nonane (9-BBN) in a solvent such
as THF, then with an aqueous alkaline solution such as potassium
phosphate in water, a palladium catalyst such as
[1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)
(Cl.sub.2Pd(dppf)), and an alkenyl or aryl halide such as vinyl
bromide or bromobenzene and a solvent such as DMF at a temperature
of about 50.degree. C. Compounds of Formula 4.2, where R.sub.1 is
as originally defined, can be obtained from compounds of Formula
4.0, where R.sub.1 is as previously defined, by treating with 9-BBN
in a solvent such as THF followed by an oxidizing agent such as an
aqueous hydrogen peroxide (H.sub.2O.sub.2) solution, as shown in c.
Alternatively, alcohols of Formula 4.3, where R.sub.1 is as
originally defined, can be obtained by subjecting compounds of
Formula 4.0, where R.sub.1 is as previously defined, to ozone in a
solvent mixture such as DCM and MeOH at a temperature such as
-78.degree. C. and then quenching with a reducing agent such as
sodium borohydride (NaBH.sub.4), as depicted in d. Alcohols of
Formula 4.2 and 4.3, where R.sub.1 is as previously defined, can be
arylated using an arylating agent such as
diacetoxy(triphenyl)bismuth, a catalyst such as diacetoxycopper,
and a base, such as N,N-dicyclohcxylmethylamine, in a solvent such
as toluene at a temperature of about 60.degree. C. or alkylated by
treating with a base such as NaH and an alkyl halide such as methyl
iodide (iodomethane, MeI) in as solvent such as THF to afford
compounds of Formula 4.4 and 4.5, where R.sub.1 is as originally
defined and R.sub.6 is aryl or alkyl, as depicted in e.
##STR00007##
[0068] Compounds of Formula 5.2, where R.sub.1 and R.sub.2 are as
originally defined, can be prepared according to the methods
outlined in Scheme 5, steps a-b. As shown in a, compounds of
Formula 5.0, where R.sub.1 and R.sub.2 are as originally defined,
can be treated with a Lewis acid such as lithium tetrafluoroborate
(LiBF.sub.4) in a polar, aprotic solvent such as CH.sub.3CN at a
temperature of about 60.degree. C. to obtain aldehydes of Formula
5.1, where R.sub.1 and R.sub.2 are as originally defined. Compounds
of Formula 5.2, where R.sub.1 and R.sub.2 are as previously
defined, can be prepared from aldehydes of Formula 5.1, where R and
R.sub.2 are as previously defined, by treating with an ylide
precursor such as methyl
2-((tert-butoxycarbonyl)amino)-2-(dimethoxyphosphoryl)acetate and a
base such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in a solvent
such as DCM to afford compounds of Formula 5.2, where R.sub.1 and
R.sub.2 are as previously defined, as shown in b.
##STR00008##
[0069] Compounds of Formula 6.2, where R.sub.1 and R.sub.2 are as
originally defined, but R.sub.2 is not alkenyl, can be prepared
according to the methods outlined in Scheme 6, steps a-c. Compounds
of Formula 5.2, where R.sub.1 and R.sub.2 are as originally
defined, can be treated with a chiral catalyst such as
(+)-1,2-bis((2S,5S)-2,5-diethylphospholano)benzene(1,5-cyclooctadiene)rho-
dium(I) trifluoromethanesulfonate in the presence of H.sub.2, to
afford, compounds of Formula 6.0, where R.sub.1 and R.sub.2 are as
originally defined, but R.sub.2 is not alkenyl, as shown in a.
Compounds of Formula 6.1, where R.sub.1 and R.sub.2 are as
originally defined, can be obtained from compounds of Formula 6.0,
where R.sub.1 and R.sub.2 are as previously defined, by treating
with an oxidant such as 2,3-dichloro-5,6-dicyano-p-benzoquinone
(DDQ) in a solvent mixture such as DCM and water, as shown in b.
Treating compounds of Formula 6.1, where R.sub.1 and R.sub.2 are as
previously defined, with a hydroxide base such as lithium hydroxide
(LiOH) in a solvent mixture such as THF and water, as depicted in
c, provides compounds of Formula 6.2, where R.sub.1 and R.sub.2 are
as previously defined,
##STR00009##
[0070] Compounds of Formula 7.0, where R.sub.1 and R.sub.2 are as
originally defined, can be prepared according to the method
outlined in Scheme 7, step a. Compounds of Formula 7.0, where
R.sub.1 and R.sub.2 are as previously defined, can be obtained by
the addition of a solution of compounds of Formula 6.2, where
R.sub.1 and R.sub.2 are as originally defined, in a halogenated
solvent such as DCM to a mixture of a base, such as
4-dimethylaminopyridine (DMAP), and a mixed anhydride, such as
2-methyl-6-nitrobenzoic anhydride (MNBA), in an aprotic solvent
such as DCM over a period of 4-12 hours (h), as shown in a.
##STR00010##
[0071] Compounds of Formula 8.2, where R.sub.1 is as originally
defined and R.sub.6 is acyl, can be prepared according to the
method outlined in Scheme 8, steps a-b. Compounds of Formula 8.1,
where R.sub.1 is as originally defined, can be prepared from
compounds of Formula 8.0, where R.sub.1 is as originally defined,
by treating with a catalyst such as Pd/C in the presence of H.sub.2
in a solvent such as EtOAc as shown in a. Alcohols of Formula 8.1,
where R.sub.1 is as previously defined, can be acylated with an
acylating agent such as isobutryl chloride in the presence of a
base such as triethylamine (NEt.sub.3) and a catalyst such as DMAP
in a halogenated solvent such as DCM, as depicted in b, to afford
compounds of Formula 8.2, where R.sub.1 and R.sub.6 are as
previously defined.
##STR00011##
[0072] Compounds of Formula 9.1, where R.sub.1 and R.sub.2 are as
originally defined, can be prepared through the methods shown in
Scheme 9, steps a-b. Compounds of Formula 7.1, where R.sub.1 and
R.sub.2 are as originally defined, can be treated with an acid such
as a 4N solution of hydrogen chloride (HCl) in dioxane in a
halogenated solvent such as DCM to afford compounds of Formula 9.0,
where R.sub.1 and R.sub.2 are as originally defined, as depicted in
a. The resulting hydrochloride salt may be neutralized prior to use
to give the free amine or neutralized in situ in step b. Compounds
of Formula 9.1, where R.sub.1 and R.sub.2 are as originally
defined, can be prepared from compounds of Formula 9.0, where
R.sub.1 and R.sub.2 are as defined above, by treating with
3-hydroxy-4-methoxypicolinic acid in the presence of a base, such
as diisopropylethylamine, and a peptide coupling reagent, such as
benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate
(PyBOP) or O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium
hexafluorophosphate (HATU), in an halogenated solvent such as DCM,
as shown in b.
##STR00012##
[0073] Compounds of Formula 10.0, where R.sub.1, R.sub.2, and
R.sub.4 are as originally defined, can be prepared according to the
method outlined in Scheme 10. Compounds of Formula 10.0, where
R.sub.1, R.sub.2, and R.sub.4 are as defined above, can be prepared
from compounds of Formula 9.1, where R.sub.1 and R.sub.2 are as
originally defined, by treatment with the appropriate alkyl halide
with or without a reagent such as sodium iodide (NaI) and an alkali
carbonate base such as sodium carbonate (Na.sub.2CO.sub.3) or
potassium carbonate (K.sub.2CO.sub.3) in a solvent such as acetone
or by treatment with an acyl halide in the presence of an amine
base, such as pyridine, TEA, DMAP, or mixtures thereof in an
aprotic solvent such as DCM, as shown in a.
##STR00013##
Examples
Example 1, Step 1: Preparation of (S)-methyl
2-((S)-1-hydroxyethyl)-5-methylhex-4-enoate
##STR00014##
[0075] To a solution of diisopropylamine (19.9 milliliter (mL), 142
millimoles (mmol)) in anhydrous THF (99 mL) at -50.degree. C.
(deficient dry ice/acetone bath) was added n-butyllithium (n-BuLi;
54.3 mL, 130 mmol, 2.5 M in hexanes). This solution was removed
from the cold bath for 15 minutes (min), then re-cooled to
-50.degree. C. To the LDA was added a solution of (S)-methyl
3-hydroxybutanoate (6.64 mL, 59.3 mmol) in THF (20.0 mL) dropwise
over 15 min using a cannula. This solution was allowed to warm to
-30.degree. C. over 30 min, stirred at -30.degree. C. for 1 hour
(h), and recooled to -78.degree. C. To the enolate was added a
solution of 1-bromo-3-methylbut-2-ene (13.7 mL, 119 mmol) in
anhydrous 1,2-dimethoxyethane (20.0 mL, 193 mmol) dropwise over 15
min. The cold bath was at -60.degree. C. after 1 h at which time
the reaction flask was removed from the bath and the mixture
stirred without cooling for 1.5 h. The reaction mixture was
quenched by the addition of saturated (sat.) aqueous (aq.) ammonium
chloride (NH.sub.4Cl; 50 mL), diluted with EtOAc (50 mL), and the
phases were separated. The aqueous phase was further extracted with
EtOAc (2.times.50 mL) and the combined organic extracts were washed
with sat. aq. sodium chloride (NaCl, brine; 50 mL), dried over
sodium sulfate (Na.sub.2SO.sub.4), filtered, and concentrated to
dryness. The crude residue was purified by flash column
chromatography (silica gel (SiO.sub.2), 0.fwdarw.40% EtOAc in
hexanes) to afford the title compound (9.5 g, 86%) as a slightly
yellow oil; IR (thin film) 3452, 2971, 2929, 1730, 1437, 1198, 1160
cm.sup.-1; .sup.1H NMR (400 MI-Hz, CDCl.sub.3) .delta. 5.11-5.01
(m, 1H), 3.92 (p, J=6.3 Hz, 1H), 3.70 (s, 3H), 2.78 (s, 1H),
2.46-2.28 (m, 3H), 1.69 (d, J=1.4 Hz, 3H), 1.62 (s, 3H), 1.23 (d,
J=6.4 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 175.54,
134.14, 120.30, 67.78, 52.72, 51.52, 27.90, 25.73, 21.46,
17.64.
Example 1, Step 2: Preparation of(S)-methyl
2-((S)-1-hydroxyethyl)-5-methylhexanoate
##STR00015##
[0077] To a well stirred solution of (S)-methyl
2-((S)-1-hydroxyethyl)-5-methylhex-4-enoate (9.5 g, 51.0 mmol) in
MeOH (51 mL) was added 10% Pd/C (0.543 g, 5.10 mmol). The reaction
mixture was put under an H.sub.2 atmosphere (balloon) and stirred
at room temperature for 20 h. The mixture was filtered through a
plug of Celite.RTM. and the plug was washed with MeOH (20 mL). The
filtrate and washes were combined, the solvent was removed under
reduced pressure, and the residue was dissolved in DCM (50 mL.).
The solution was passed through a phase separator to remove
residual water (H.sub.2O), and the solvent was removed under
reduced pressure to afford the title compound (9.45 g, 98%) as a
slightly yellow oil: IR (thin film) 3451, 2954, 2871, 1736, 1719,
1169 cm.sup.-1; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 3.91 (p,
J=6.4 Hz, 1H), 3.72 (s, 3H), 2.77 (s, 1H), 2.36 (ddd, J=9.2, 6.3,
5.0 Hz, 1H), 1.72-1.45 (m, 3H), 1.28-1.05 (m, 51H), 0.88 (dd,
J=6.6, 3.2 Hz, 6H); .sup.13C NMR (75 MHz, CDCl.sub.3) .delta.
176.13, 68.55, 53.29, 51.67, 36.55, 28.16, 27.37, 22.74, 22.44,
21.68.
Example 1, Step 3: Preparation of(S)-methyl
2-((S)-1-((4-methoxybenzyl)oxy)ethyl)-5-methylhexanoate
##STR00016##
[0079] To a solution of(S)-methyl
2-((S)-1-hydroxyethyl)-5-methylhexanoate (5.00 g, 26.6 mmol) and
CSA (0.617 g, 2.66 mmol) in DCM (53.1 mL) was added 4-methoxybenzyl
2,2,2-trichlomacetimidate (8.27 mL, 39.8 mmol) at 0.degree. C. The
reaction mixture was removed from the cold bath and stirred at room
temperature for 17 h. Hexane (50 mL) was added to the reaction
mixture and the precipitate was removed by filtration. The solids
were washed with hexanes (2.times.10 mL), and Celite.RTM. was added
to the combined filtrate and washes and the solvent was removed
under reduced pressure. The resulting adsorbed material was
directly loaded onto a column and purified using flash column
chromatography (SiO.sub.2.fwdarw.35% EtOAc in hexanes) to afford
the title compound (6.3 g, 77%) as a colorless oil: .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta.7.24-7.16 (m, 2H), 6.89-6.79 (m, 2H),
4.49 (d, J=11.2 Hz, 1H), 4.33 (d, J=11.1 Hz, 1H), 3.75 (s, 3H),
3.74-3.62 (m, 4H), 2.49 (ddd, J=10.7, 8.2, 4.0 Hz, 1H), 1.62-1.40
(m, 3H), 1.23-1.16 (m, 3H), 1.16-1.03 (m, 2H), 0.87 (d, J=3.9 Hz,
3H), 0.85 (d. J=3.9 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3)
.delta. 175.03, 159.10, 130.63, 129.14, 113.62, 76.16, 70.71,
55.11, 52.64, 51.25, 36.58, 27.97, 26.00, 22.69, 22.17, 17.08;
ESIMS m/z 331 ([M+Na].sup.+).
Example 2, Steps 1 and 2: Preparation of
(3S,4R)-4-((S)-1-((4-methoxy-benzyl)oxy)ethyl)-7-methyloct-1-en-3-ol
and
(3R,4R)-4-((S)-1-((4-methoxybenzyl)oxy)ethyl)-7-methyloct-1-en-3-ol
##STR00017##
[0080] Step 1
[0081] To a solution of (S)-methyl
2-((S)-1-((4-methoxybenzyl)oxy)ethyl)-5-methylhexanoate (6.00 g,
19.5 mmol) and chlorobis(cyclooctene)-iridium(I) dimer (0.349 g,
0.389 mmol) in dry DCM (19.5 mL) was slowly added Et.sub.2SiH.sub.2
(3.76 mL, 29.2 mmol) at 0.degree. C. The flask was removed from the
cold bath and the reaction mixture was stirred at room temperature
for 20 h under nitrogen (N.sub.2). The reaction mixture was
transferred via cannula to an ice-cooled mixture of diethyl ether
(Et.sub.2O; 60 mL) and 2 Normal (N) aq. hydrogen chloride (HCl; 20
mL) over a 15 min period. The mixture was removed from the cold
bath and stirred at room temperature for 30 min. The phases were
separated and the aq. phase was further extracted with Et.sub.2O
(2.times.50 mL). The organics were combined, washed with sat. aq.
sodium bicarbonate (NaHCO.sub.3; 25 mL) and brine (25 mL), dried
over Na.sub.2SO.sub.4, filtered, and the filtrate treated with
Celite.RTM.. The solvent was removed under reduced pressure and the
resulting adsorbed material was directly loaded onto a column and
purified using flash column chromatography (SiO.sub.2, 0-75% EtOAc
in hexanes) to afford the intermediate aldehyde,
(S)-2-((S)-1-((4-methoxybenzyl)oxy)ethyl)-5-methylhexanal.
Step 2
[0082] The intermediate aldehyde was dissolved in THF (30 mL) and
the mixture was cooled to -78.degree. C. and treated dropwise with
vinylmagnesium bromide (29.2 mL, 29.2 mmol, 1M in THF). The
resulting solution was stirred at -78.degree. C. for 30 min,
removed from the cold bath, warmed to and stirred at room
temperature for 30 min, and then quenched by the addition of sat.
aq. NH.sub.4Cl (30 mL). The phases were separated and the aq. phase
was further extracted with Et.sub.2O (3.times.50 mL). The combined
organics were dried over Na.sub.2SO.sub.4, filtered, and
concentrated to dryness. The residue was dissolved in DCM (20 mL)
and the resulting solution was treated with Celite.RTM.. The
solvent was removed under reduced pressure and the resulting
adsorbed material was directly loaded onto a column and purified
using flash column chromatography (SiO.sub.2, 0.fwdarw.15% acetone
in hexanes) to afford the individual diastercomers as colorless
oils:
[0083]
(3S,4R)-4-((S)-1-((4-methoxybenzyl)oxy)ethyl)-7-methyloct-1-en-3-ol
(2.35 g, 39%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.27-7.19
(m, 2H), 6.91-6.82 (m, 2H), 5.84 (ddd, J=17.2, 10.6, 4.7 Hz, 1H),
5.29 (apparent (app) dt, J=17.2, 1.9 Hz, 1H), 5.16 (app dt, J=10.6,
1.9 Hz, 1H), 4.58 (d, J=11.0 Hz, 1H), 4.53-4.45 (m, 1H), 4.27 (d,
J=10.9 Hz, 1H), 3.83 (d, J=4.3 Hz, 1H), 3.79 (s, 3H), 3.76-3.65 (m,
1H), 1.52-1.26 (m, 7H), 1.20-1.06 (m, 2), 0.85 (app dd, J=6.6, 2.2
Hz, 6H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 159.33, 139.16,
130.02, 129.54, 114.61, 113.88, 76.55, 72.08, 70.65, 55.26, 49.31,
37.35, 28.25, 23.51, 22.63, 22.52, 17.71; ESIMS n/z 329
([M+Na].sup.+).
[0084]
(3R,4R)-4-((S)-1-((4-methoxybenzyl)oxy)ethyl)-7-methyloct-1-en-3-ol
(1.48 g, 25%): .sup.1H-NMR (400 MHz, CDCl.sub.3) .delta. 7.30-7.22
(m, 2H), 6.91-6.83 (m, 2H), 5.89 (ddd, J=17.1, 10.3, 6.7 Hz, 1H),
5.24 (ddd, J=17.2, 1.8, 1.2 Hz, 1H), 5.12 (ddd, J=10.4, 1.8, 1.1
Hz, 1H), 4.58 (d, J=11.1 Hz, 1H), 4.35 (d, J=11.1 Hz, 1H),
4.22-4.13 (m, 1H), 3.80 (s, 3H), 3.70 (p, J=6.3 Hz, 1H), 3.66 (d,
J=3.2 Hz, 1H), 1.56 (tt, J=6.8, 5.2 Hz, 1H), 1.49-1.24 (m, 6H),
1.19-1.08 (m, 2H), 0.84 (dd, J=6.7, 2.0 Hz, 6H); .sup.13C NMR (101
MHz, CDCl.sub.3) .delta. 159.24, 140.20, 130.22, 129.41, 115.17,
113.87, 78.10, 75.83, 70.43, 55.28, 48.98, 36.07, 28.53, 26.08,
22.52, 17.93; ESIMS m/z 329 ([M+Na].sup.+).
Example 2, Steps 3 and 4: Preparation of
(2R,3R,4S)-3-benzyl-4-((4-methoxybenzyl)oxy)-1-phenylpentan-2-ol
##STR00018##
[0086] To a solution of
(3R,4S)-3-benzyl-4-(4-methoxybenzyl)oxy)-1-phenylpentan-2-ol (3.1
g, 7.94 mmol) in DCM (31.8 mL) was added NaHCO.sub.3 (0.767 g, 9.13
mmol) and the reaction was cooled to 0.degree. C. and treated with
DMP (3.87 g, 9.13 mmol). The flask was removed from the cold bath,
allowed to warm to room temperature, and stirred for 3 h. The
reaction mixture was diluted with DCM and quenched with a half sat
aq. solution of sodium thiosulfate (Na.sub.2S.sub.2O.sub.3). The
biphasic mixture was stirred for 5 min, during which time the
layers became clear. The aqueous phase was extracted DCM (2.times.)
and then the combined organic phases were washed with sat. aq.
NaHCO.sub.3 and dried by passing through a phase separator
cartridge. The solvent was removed and the crude oil was purified
by flash column chromatography (SiO.sub.2, 1.fwdarw.20% acetone in
hexanes) to afford the intermediate ketone,
(3S,4S)-3-benzyl-4-((4-methoxybenzyl)oxy)-1-phenylpentan-2-one,
(2.28 g, 74%) as a colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 729-7.22 (m, 3H), 722-7.19 (m, 1H), 7.17 (ddd, J=5.5, 2.5,
1.1 Hz, 4H), 7.10-7.05 (m, 2H), 6.89-6.81 (m, 2H), 6.74-6.70 (m,
2H), 4.48 (d, J=10.8 Hz, 1H), 4.26 (d, J=10.8 Hz, 1H), 3.80 (s,
3H), 3.85-3.73 (m, 1H), 3.53 (d, J=172 Hz, 1H), 3.14 (d, J=17.1 Hz,
1H), 3.09 (ddd, J=10.8, 8.5, 4.7 Hz, 1H), 2.81 (dd, J=13.0, 10.7
Hz, 1H), 2.75 (dd, J=13.1, 4.8 Hz, 1H), 1.30 (d, J=6.1 HK, 3H);
.sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 210.45, 159.19, 139.07,
133.70, 130.43, 129.76, 129.45, 129.02, 128.54, 128.18, 126.55,
126.33, 113.75, 77.21, 71.10, 59.67, 55.29, 53.08, 34.91, 17.51;
ESIMS min 411 ([M+Na].sup.+).
[0087] To a solution of
(3S,4S)-3-benzyl-4-((4-methoxybenzyl)oxy)-1-phenylpentan-2-one (1.5
g, 3.86 mmol) in toluene (25.7 mL) was added
(S)-1-methyl-3,3-diphenylhexahydropyrrolo-[1,2-c][1,3,2]oxazaborole
(0.386 mL, 0.386 mmol) followed by the slow addition of a solution
of BH.sub.3-DMS (0.403 mL, 4.25 mmol) in toluene (5 mL) at room
temperature. The reaction mixture was stirred for 3 h, quenched
with MeOH (3.12 mL, 77 mmol), and partitioned between EtOAc and
water. The phases were separated and the aqueous phase was
extracted with EtOAc (2.times.). The combined organic phases were
washed with brine, dried over Na.sub.2SO.sub.4, filtered,
concentrated, and the crude oil purified by flash column
chromatography (SiO.sub.2, I.fwdarw.20% acetone in hexanes) to
afford the title compound (878 mg, 58%) as a colorless oil: .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 7.30-7.24 (m, 6H), 7.23-7.17 (m,
2H), 7.16-7.08 (m, 4H), 6.92-6.86 (m, 2H), 4.58 (d, J=11.3 Hz, 1H),
4.34 (d, J=11.3 Hz, 1H), 4.05-3.91 (m, 1H), 3.81 (s, 3H), 3.76 (qd,
J=6.4, 4.0 Hz, 1H), 2.96 (dd, J=13.8, 3.4 Hz, 1H), 2.83 (dd,
J=12.3, 5.8 Hz, 1H), 2.81-2.75 (m, 1H), 2.69 (dd, J.ltoreq.13.8,
9.7 Hz, 1H), 2.31 (d, J=4.2 Hz, 1H), 2.04 (tt, J=7.1, 4.3 Hz, 1H),
1.30 (d, J=6.4 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) .delta.
159.15, 141.29, 139.47, 130.82, 129.30, 129.20, 129.17, 128.47,
128.32, 126.25, 125.80, 113.84, 75.10, 73.54, 70.33, 55.31, 50.02,
42.21, 34.15, 18.21; ESIMS m/z 413 ([M+Na].sup.+).
Example 2, Step 5a: Preparation of
(2R,3S)-2-benzyl-3-((4-methoxybenzyl)-oxy)butan-1-ol
##STR00019##
[0089] To a solution of (2S,3S)-methyl
2-benzyl-3-((4-methoxybenzyl)oxy)butanoate (1 g, 3.05 mmol) in THF
(15.2 mL) at 0.degree. C. was added LAH (3.20 mL, 3.20 mmol, 1 M in
THF). The reaction was left to stir at 0.degree. C. for 2 h, then
removed from the cold bath and let warm to room temperature for 1
h. The flask was cooled to 0.degree. C. and the mixture was diluted
with EtOAc (15 mL) and quenched with a sat, aq. solution of
Rochelle's salt (.about.30 mL). The biphasic mixture was removed
from the cold bath and stirred over the weekend, at which point the
phases became clear. The phases were separed and the aqueous phase
was extracted with EtOAc (3.times.). The combined organic phases
were washed with brine and dried over Na.sub.2SO.sub.4 and
filtered. The solvent was evaporated and the crude oil was purified
by flash chromatography (SiO.sub.2, 1.fwdarw.30% acetone in
hexanes) to afford the title compound (788 mg, 86%) as a colorless
oil: .sup.1H NMR (400 MHz, CDCl) .delta. 7.31-7.22 (m, 4H),
7.22-7.17 (m, 1H), 7.16-7.10 (m, 2H), 6.92-6.86 (m, 2H), 4.60 (d,
J=11.2 Hz, 1H), 4.31 (d, J=11.2 Hz, 1H), 3.90 (ddd, J=11.3, 3.9,
2.6 Hz, 1H), 3.82 (s, 3H), 3.67 (qd, J=6.1, 4.2 Hz, 1H), 3.51 (ddd,
J=11.3, 7.6, 4.9 Hz, 1H), 2.86 (dd, J=7.5, 3.9 Hz, 1H), 2.80 (dd,
J=13.7, 6.6 Hz, 1H), 2.73 (dd, J=13.7, 8.4 Hz, 1H), 1.76 (ddtd,
J=9.0, 7.0, 4.6, 2.5 Hz, 1H), 1.31 (d, J=6.2 Hz, 3H); .sup.13C NMR
(101 MHz, CDCl.sub.3) .delta. 159.29, 140.56, 130.29, 12937,
129.17, 128.34, 125.95, 113.90, 77.45, 70.69, 62.37, 55.30, 47.79,
35.15, 17.68; ESIMS m/z 323 ([M+Na].sup.+).
Example 2, Step 5b: Preparation of
(2R,3S)-2-isopentylbutane-1,3-diol
##STR00020##
[0091] To a solution of(S)-methyl
2-((S)-1-hydroxyethyl)-5-methylhexanoate (1 g, 5.31 mmol) in THF
(21.3 mL) at 0.degree. C. was added LAH (5.84 mL, 5.84 mmol, 1M in
THF). The reaction mixture was left to stir at 0.degree. C. for 10
min, removed from the cold bath, and allowed to warm to room
temperature. After stirring for 3 h, H.sub.2O (0.222 mL), 15% aq.
NaOH (0.222 mL), H.sub.2O (0.666 mL), and then Et.sub.2O (25 mL)
were sequentially added to the reaction flask. The mixture was
stirred vigorously at room temperature for 1 h, MgSO.sub.4 was
added, and the suspension was filtered through a pad of
Celite.RTM.. The pad was washed with Et.sub.2O (3.times.20 mL) and
the filtrate and washings were combined and concentrated under
reduced pressure to afford the title compound (825 mg, 97%) as a
colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 3.96-3.82
(m, 2H), 3.71-3.61 (m, 1H), 2.96 (t, J=5.2 Hz, 1H), 2.82 (d, J=4.1
Hz, 1H), 1.60-1.08 (m, 9H), 0.89 (app dd, J=6.6, 3.8 Hz, 6H):
.sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 72.19, 64.67, 46.51,
36.42, 28.31, 26.26, 22.72, 22.37, 22.16.
Example 3, Step 1a: Preparation of
((2R,3S)-2-(allyloxy)-3-((S)-1-((4-methoxybenzyl)oxy)ethyl)butane-1,4-diy-
l)dibenzene
##STR00021##
[0093] To a solution of
(2R,3R,4S)-3-benzyl-4-((4-methoxybenzyl)oxy)-1-phenylpentan-2-ol
(878 mg, 2.25 mmol) in DMF (9 mL) at 0.degree. C. was added a 60%
dispersion of NaH (225 mg, 5.62 mmol) in mineral oil. The reaction
mixture was stirred at 0.degree. C. for 5 min, treated with
3-bromoprop-1-ene (535 microliters (.mu.L), 6.18 mmol), removed
from the cold bath, and then heated to 50.degree. C. The reaction
mixture was maintained at 50.degree. C. for 5 h, cooled to room
temperature, diluted with EtOAc, and quenched with sat. aq.
NH.sub.4Cl. The phases were separated and the aqueous phase was
extracted with EtOAc (2.times.). The combined organic phases were
washed with brine (4.times.), dried over Na.sub.2SO.sub.4,
filtered, and the solvent evaporated. The residual colorless oil
was purified by flash chromatography (SiO.sub.2, 1.fwdarw.20%
acetone in hexanes) to give the title compound (782 mg, 81%) as a
colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.29-7.24
(m, 3H), 7.24-7.20 (m, 3H), 7.18 (dt, J=2.9, 1.5 Hz, 1H), 7.17-7.13
(m, 1H), 7.15-7.03 (m, 4H), 6.92-6.84 (m, 2H), 5.74 (ddt, J=17.2,
10.6, 5.4 Hz, 1H), 5.15 (dq, J=17.2, 1.7 Hz, 1H), 5.05 (dq, J=10.4,
1.5 Hz, 1H), 4.50 (d, J=11.3 Hz, 1H), 4.29 (d, J=11.3 Hz, 1H),
3.87-3.81 (m, 1H), 3.81 (s, 3H), 3.79-3.74 (m, 1H), 3.74-3.69 (m,
2H), 2.97 (dd, J=13.9, 4.4 Hz, 1H), 2.89 (dd, J=13.6, 6.5 Hz, 1H),
2.79 (dd, J=13.5, 7.6 Hz, 1H), 2.76 (dd, J=13.9, 8.8 Hz, 1H), 2.10
(tdd, J=6.6, 5.3, 3.6 Hz, 1H), 1.25 (d, J=6.3 Hz, 3H); .sup.13C NMR
(101 MHz, CDCl.sub.3) .delta. 159.00, 141.94, 140.22, 135.34,
131.27, 129.33, 129.18, 128.99, 128.21, 128.09, 125.81, 125.59,
115.96, 113.75, 79.99, 73.77, 70.99, 70.17, 55.31, 48.07, 38.38,
31.83, 17.68; ESIMS m/z 453 ([M+Na].sup.+).
Example 3, Step 1b: Preparation of
(2S,3R)-3-((allyloxy)methyl)-6-methylheptan-2-ol
##STR00022##
[0095] To a suspension of NaH (404 mg, 10.1 mmol, 60% dispersion in
mineral oil) in anhydrous THF (20 mL) was added a solution of
(2R,3S)-2-isopentylbutane-1,3-diol (810 mg, 5.05 mmol) in THF (9
mL) dropwise at 0.degree. C. The mixture was removed from the cold
bath and stirred at room temperature for 30 minutes, recooled to
0.degree. C., and then treated with 3-bromoprop-1-ene (416 .mu.L,
4.81 mmol). After 4 h, DMF (3.2 mL) was added to the reaction and
the mixture was maintained at mom temperature for 14 h. The
reaction mixture was quenched with sat. aq. NH.sub.4Cl (20 mL) and
extracted with Et.sub.2O (3.times.20 mL). The combined organic
extracts were washed with brine (15 mL), dried (Na.sub.2SO.sub.4),
filtered, and concentrated to dryness. The crude residue was
purified by flash chromatography (SiO.sub.2, 0.fwdarw.25% EtOAc in
hexanes) to give the title compound (425 mg, 44%) as a colorless
oil: .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 5.89 (ddt, J=17.3,
10.4, 5.6 Hz, 1H), 5.27 (dq. J=17.3, 1.6 Hz, 1H), 5.19 (dq, J=10.4,
1.4 Hz, 1H), 3.98 (ddt, J=5.8, 3.0, 1.4 Hz, 2H), 3.86-3.77 (m, 1H),
3.69 (dd, J=9.4, 3.5 Hz, 1H), 3.47 (dd, J=9.4, 6.6 Hz, 1H),
3.32-3.26 (m, 1H), 1.57-1.37 (m, 31H), 1.34-1.14 (m, 6H), 0.88 (app
dd, J=6.6, 3.7 Hz, 6): .sup.13C NMR (101 MHz, CDCl.sub.3) .delta.
134.31, 117.18, 72.46, 72.29, 70.99, 44.98, 36.47, 28.32, 26.43,
22.73, 22.39, 21.48.
Example 3, Step 2: Preparation of
2-(((2R,3S,4S)-3-benzyl-4-((4-methoxybenzyl)-oxy)-1-phenylpentan-2-yl)oxy-
)acetaldehyde
##STR00023##
[0097] To a solution of
((2R,3S)-2-(allyloxy)-3-((S)-1-((4-methoxybenzyl)oxy)ethyl)butane-1,4-diy-
l)dibenzene (772 mg, 1.79 mmol) in DCM (16.3 mL) and MeOH (1.63
mL), was added NaHCO.sub.3 (30.1 mg, 0.359 mmol) and Sudan 111 (10
.mu.L, 1.79 mmol, 10% solution in DCM). The flask was connected to
an ozonator and cooled to -78.degree. C. and ozone was bubbled into
the flask until the color turned from red to colorless (.about.10
min). The introduction of ozone was stopped and O.sub.2 was bubbled
through the reaction mixture to purge any remaining ozone for
(.about.5 min). While still at -78.degree. C., Ph.sub.3P (705 mg,
2.69 mmol) was added in one portion and the flask was removed from
the cold bath, fitted to a nitrogen balloon, and let warm to room
temperature overnight. A scoop of Celite.RTM. was added to the
mixture, the majority of the solvent was evaporated, and the
resulting slurry was purified by flash column chromatography
(SiO.sub.2, 1.fwdarw.20% acetone in hexanes) to afford the title
compound (730 mg, 94%) as a colorless oil: .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 9.39 (d, J=1.0 Hz, 1H), 7.31-7.19 (m, 6H),
7.21-7.15 (m, 2H), 7.15-7.10 (m, 2H), 7.08 (dd, J=7.6, 1.3 Hz, 2H),
6.91-6.86 (m, 2H), 4.54 (d, J=11.3 Hz, 1H), 4.29 (d, J=11.3 Hz,
1H), 3.81 (d, J=0.6 Hz, 3H), 3.81-3.79 (m, 1H), 3.76 (dt, J=9.4,
3.5 Hz, 1H), 3.73-3.72 (m, 1H), 3.72-3.66 (m, 1H), 3.04 (dd,
J=14.0, 3.6 Hz, 1H), 2.93 (dd, J=13.8, 6.3 Hz, 1H), 2.83-2.75 (m,
2H), 2.22-2.04 (m, 1H), 1.25 (d, J=6.4 Hz, 3H); .sup.13C NMR (101
MHz, CDCl.sub.3) .delta. 201.77, 159.09, 141.43, 139.70, 131.00,
129.29, 129.10, 129.07, 128.34, 128.34, 126.19, 125.82, 113.80,
82.70, 75.95, 73.68, 70.28, 55.31, 48.62, 38.45, 32.06, 17.82;
ESIMS m/z 455 ([M+Na].sup.+).
Example 3, Step 3: Preparation of methyl
4-(((2R,3S,4S)-3-benzyl-4-((4-methoxybenzyl)oxy)-1-phenylpentan-2-yl)oxy)-
-2-((tert-butoxycarbonyl)amino)but-2-enoate
##STR00024##
[0099] To a solution of
2-(((2R,3S,4S)-3-benzyl-4-((4-methoxybenzyl)oxy)-1-phenylpentan-2-yl)oxy)-
acetaldehyde (725 mg, 1.68 mmol) in DCM (13.5 mL) was added methyl
2-((tert-butoxycarbonyl)amino)-2-(dimethoxyphosphoryl)acetate (508
mg, 1.71 mmol), and the reaction mixture was cooled to 0.degree. C.
and treated with DBU (0.203 mL, 1.76 mmol). The vial was sealed and
allowed to slowly warm to room temperature overnight as the ice
melted. The reaction mixture was quenched with sat. aq. NH.sub.4Cl,
the phases were separated, and the aqueous phase was extracted with
DCM (3.times.). The combined organic phase was dried by passing
through a phase separator cartridge and the solvent was evaporated.
The resulting oil was purified by flash column chromatography
(SiO.sub.2, 1.fwdarw.15% acetone in hexanes) to afford the title
compound (818 mg, 81%) as a colorless oil: .sup.1H NMR (400 MHz,
CDCl.sub.3) major isomer .delta. 7.30-7.23 (m, 4H), 7.24-7.20 (m,
3H), 7.19-7.16 (m, 1H), 7.12-7.02 (m, 4H), 6.88 (d, J=8.6 Hz, 2H),
6.31 (s, 1H), 6.25 (t, J=5.8 Hz, 1H), 4.51 (d, J=11.3 Hz, 1H), 428
(d, J=11.3 Hz, 1H), 4.03 (dd, J=14.9, 5.7 Hz, 1H), 3.89 (dd,
J=14.8, 5.9 Hz, 1H), 3.81 (s, 3H), 3.78 (s, 3H), 3.74-3.65 (m, 2H),
2.99 (dd, J=14.0, 4.1 Hz, 1H), 2.87 (dd, J=13.7, 6.4 Hz, 1H), 2.78
(dd, J=13.6, 7.7 Hz, 1H), 2.73 (dd, J=13.9, 8.8 Hz, 1H), 2.15-2.02
(m, 1H), 1.43 (s, 9H), 1.23 (d, J=6.3 Hz, 3H); .sup.13C NMR (101
MHz, CDCl.sub.3) major isomer, (two aromatic signals overlap)
.delta. 164.97, 159.01, 152.95, 141.66, 139.99, 131.17, 129.25,
129.15, 129.02, 128.25, 128.18, 125.88, 125.66, 113.75, 80.86,
80.77, 73.62, 70.18, 66.70, 55.30, 52.46, 48.11, 38.35, 31.94,
28.13, 17.74; ESIMS m/z 626 ([M+Na].sup.+).
Example 4, Step 1: Preparation of
1-((2S,3R)-3-(2,2-diethoxyethoxy)-2-((S)-1-((4-methoxybenzyl)oxy)ethyl)pe-
nt-4-en-1-yl)-4-fluorobenzene
##STR00025##
[0101] To a solution of
(3R,4R,5S)-4-(4-fluorobenzyl)-5-((4-methoxybenzyl)oxy)hex-1-en-3-ol
(711 mg, 2.06 mmol) in a mixture of CH.sub.3CN (6.88 mL) and DMF (2
mL) was added NaH (140 mg, 3.51 mmol, 60% dispersion in mineral
oil) at mom temperature. The mixture was stirred for 10 min,
treated with 2-bromo-1,1-diethoxyethane (559 .mu.L, 3.72 mmol), and
then warmed to and stirred at 55.degree. C. overnight. The reaction
mixture was cooled to room temperature, additional
2-bromo-1,1-diethoxyethane (200 .mu.L, 1.33 mmol) was added, and
the reaction mixture was again heated to 55.degree. C. and stirred
for an additional 2 h. The reaction mixture was quenched with sat.
aq. NH.sub.4Cl and the phases were separated. The aqueous phase was
extracted with EtOAc (3.times.) and the combined organic phases
were washed with brine, dried over NaSO.sub.4, filtered and then
the solvent was evaporated. The crude oil was purified by flash
column chromatography (SiO.sub.2, 1.fwdarw.15% acetone in hexanes)
to give the title compound (652 mg, 69%) as a colorless oil:
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.23 (d, J=8.6 Hz, 2H),
7.14-7.07 (m, 2H), 6.92 (t, J=8.7 Hz, 2H), 6.87 (d, J=8.6 Hz, 2H),
5.67 (ddd, J=16.7, 10.6, 7.2 Hz, 1H), 5.22-5.10 (m, 2H), 4.60 (dd,
J=5.7, 4.9 Hz, 1H), 4.45 (d, J=11.4 Hz, 1H), 4.33 (d, J=11.4 Hz,
1H), 3.80 (s, 3H), 3.77-3.63 (m, 4H), 3.63-3.48 (m, 3H), 324 (dd.
J=10.2, 5.8 Hz, 1H), 2.70 (dd, J=6.8, 2.7 Hz, 2H), 2.17-2.05 (m,
1H), 1.33-1.12 (m, 9H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-118.13; ESIMS m/z 483 ([M+Na].sup.+).
Example 4, Step 2: Preparation of
1-((2S,3R)-3-(2,2-diethoxyethoxy)-2-((S)-1-((4-methoxybenzyl)oxy)ethyl)-5-
-phenylpentyl)-4-fluorobenzene
##STR00026##
[0103] To a solution of
1-((2S,3R)-3-(2,2-diethoxyethoxy)-2-((S)-1-((4-methoxybenzyl)-oxy)ethyl)p-
ent-4-en-1-yl)-4-fluorobenzene (650 mg, 1.41 mmol) in THF (2823
.mu.L) was added 9-BBN (5363 .mu.L, 2.68 mmol, 0.5M in THF). The
flask was fitted with a Vigreux column and heated to 50.degree. C.
for 2 h. The reaction mixture was quenched with a 3 M aq. solution
of K.sub.3PO.sub.4 (847 .mu.L, 2.54 mmol), and then DMF (2823
.mu.L) and bromobenzene (PhBr; 296 .mu.L, 2.82 mmol) were added,
followed by Pd(dppf)Cl.sub.2.CH.sub.2Cl.sub.2 (103 mg, 0.126 mmol).
The vial was evacuated under vacuum and backfilled with N.sub.2
(3.times.). The mixture was then heated to and stirred at
65.degree. C. overnight, during which time the reaction turned from
homogenous orange/red solution to a nearly black solution. The
reaction mixture was cooled to room temperature, diluted with
EtOAc, and then treated with sat. aq. NaHCO.sub.3. The phases were
separated and the aq. phase was extracted with EtOAc (3.times.),
the combined organic phases were washed with brine, dried over
Na.sub.2SO.sub.4, filtered, and the solvent was evaporated. The
crude oil was purified by flash column chromatography (SiO.sub.2,
1.fwdarw.15% acetone in hexanes) to afford the title compound (759
mg, 85%): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.23 (t, J=7.8
Hz, 4H), 7.18-7.12 (m, 1H), 7.11-7.02 (m, 4H), 6.92 (t, J=8.8 Hz,
2H), 6.87 (d, J=8.6 Hz, 2H), 4.60 (t, J=5.2 Hz, 1H), 4.49 (d.
J=11.4 Hz, 1H), 4.25 (d. J=11.4 Hz, 1H), 3.80 (s, 3H), 3.73 (dt,
J=9.3, 7.0 Hz, 2H), 3.62-3.54 (m, 3H), 3.48-3.45 (m, 3H), 2.78 (dd,
J=13.7, 6.1 Hz, 1H), 2.73-2.60 (m, 2H), 2.55 (ddd, J=13.7, 9.7, 6.5
Hz, 1H), 2.12-2.01 (m, 1H), 1.93 (dddd, J=14.0, 10.3, 6.5, 4.1 Hz,
1H), 1.78 (dddd, J=13.9, 9.8, 8.3, 5.5 Hz, 1H), 1.24 (t, J=7.0 Hz,
6H), 1.11 (d, J=6.3 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta.-118.13; ESIMS m/z 561 ([M+Na].sup.+).
Example 4, Step 3: Preparation of
(3R,4S,5S)-3-(2,2-diethoxyethoxy)-4-(4-fluorobenzyl)-5-((4-methoxybenzyl)-
oxy)hexan-1-ol
##STR00027##
[0105] To neat
1-((2S,3R)-3-(2,2-diethoxyethoxy)-2-((S)-1-((4-methoxybenzyl)oxy)ethyl)-p-
ent-4-en-1-yl)-4-fluorobenzene (480 mg, 1.04 mmol) was added 9-BBN
(3127 .mu.L, 1.56 mmol, 0.5M in THF). After 4 h at room
temperature, the reaction was cooled to 0.degree. C. and treated
with 2 M NaOH (2084 .mu.L, 4.17 mmol) followed by H.sub.2O.sub.2
(426 .mu.L, 4.17 mmol, 30 weight % (wt. % in H.sub.2O). After 45
min at 0.degree. C., the cooling bath was removed and the mixture
was stirred for 30 min, recooled to 0.degree. C., and quenched with
sat. aq. NaHSO.sub.2. The phases were separated and the aqueous
phase was extracted with EtOAc (3.times.) and the combined organic
phases were washed with brine, dried over Na.sub.2SO.sub.4,
filtered, and the solvent was evaporated. The crude material was
purified by flash column chromatography (SiO.sub.2, 1.fwdarw.25%
acetone in hexanes) to afford the title compound (448 mg, 90%):
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.28-7.18 (m, 2H), 7.02
(dd, J=8.5, 5.6 Hz, 2H), 6.98-6.82 (m, 4H), 4.56 (dd J=5.9, 4.3 Hz,
1H), 4.51 (d, J=11.4 Hz, 1H), 4.19 (d, J=11.3 Hz, 1H), 3.92 (dt,
J=10.1, 3.3 Hz, 1H), 3.82 (s, 1H), 3.76-3.69 (m, 3H), 3.61-3.51 (m,
3H), 3.48-3.36 (m, 2H), 3.12 (td, J=7.6, 4.3 Hz, 1H), 2.84 (dd,
J=13.9, 4.3 Hz, 1H), 2.56 (dd, J=13.8, 9.1 Hz, 1H), 2.09-2.00 (m,
1H), 1.90-1.69 (m, 3H), 1.23 (t, J=7.1 Hz, 3H), 1.21 (t, J=6.9 Hz,
3H), 1.16 (d, J=6.3 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta.-117.92; ESIMS n/z 501 ([M+Na].sup.+).
Example 4, Step 4: Preparation of
(2S,3S,4S)-2-(2,2-diethoxyethoxy)-3-(4-fluorobenzyl)-4-((4-methoxybenzyl)-
oxy)pentan-1-ol
##STR00028##
[0107] To a solution of
1-((((2S,3S)-3-((R)-1-(2,2-diethoxyethoxy)allyl)heptan-2-yl)oxy)methyl)-4-
-methoxybenzene (1.1 g, 2.69 mmol) in DCM (20 mL) and MeOH (2 mL)
was added NaHCO.sub.3 (0.045 g, 0.538 mmol) and Sudan III indicator
(75 .mu.L of a 0.1% DCM soln). The reaction mixture was cooled to
-78.degree. C. and the flask was connected to an ozonator. Ozone
was bubbled through the solution until the solution became
colorless. Oxygen was then bubbled through the solution for 5 min
and the solution was treated with MeOH (3 mL) and NaBH.sub.4 (0.306
g, 8.08 mmol). The flask was removed from the cold bath and allowed
to slowly warm to room temperature overnight. The reaction mixture
was quenched with water (15 mL) and the phases were separated. The
aqueous phase was extracted with DCM (2.times.) and the combined
organic phases were dried over magnesium sulfate (MgSO.sub.4),
filtered, and concentrated. The crude, colorless oil was purified
by flash column chromatography (SiO.sub.2, 0.fwdarw.35% EtOAc in
hexanes) to give the title compound (0.632 g, 57%) as a colorless
oil: IR (Thin Film) 3449, 2955, 2931, 2871, 1612, 1513 cm.sup.-1;
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.26-7.20 (m, 2H),
6.89-6.84 (m, 2H), 4.63-4.58 (m, 1H), 4.51 (d, J=11.3 Hz, 1H) 4.33
(d, J=11.3 Hz, 1H), 3.80 (s, 3H), 3.78-3.51 (m, 8H), 3.49-3.38 (m,
2H), 1.74 (ddd, J=10.7, 6.1, 4.3 Hz, 1H), 1.63 (s, 1H), 1.42-1.33
(m, 2H), 1.32-1.16 (m, 13H), 0.87 (t, J=7.0 Hz, 3H); ESIMS m/z 435
([M+Na].sup.+).
Example 4, Step 5: Preparation of
1-((((2S,3S,4R)-4-(2,2-diethoxyethoxy)-3-(4-fluorobenzyl)-6-methoxyhexan--
2-yl)oxy)methyl)-4-methoxybenzene
##STR00029##
[0109] To a solution of
3R,4S,5S)-3-(2,2-diethoxyethoxy)-4-(4-fluorobenzyl)-5-((4-methoxybenzyl)o-
xy)hexan-1-ol (443 mg, 0.926 mmol) in THF (9256 .mu.l) at 0.degree.
C. was added NaH (59.2 mg, 1.48 mmol, 60 wt. % in mineral oil). The
reaction mixture was maintained at 0.degree. C. for 15 min, treated
with MeI (173 .mu.L, 2.78 mmol), removed from the cold bath, and
allowed to slowly warm to room temperature over a 2 h period.
Additional NaH (37 mg, 0.93 mmol, 60 wt. % in mineral oil) was
added at room temperature and the mixture was stirred overnight.
TLC analysis indicated that some of the alcohol starting material
(SM) still remained, so additional NaH (37 mg, 0.93 mmol, 60 wt %
in mineral oil) and MeI (86 .mu.L, 1.44 mmol) were added and
stirring was continued for another 1 h. The reaction mixture was
quenched with sat. aq. NH.sub.4Cl and the phases were separated.
The aqueous phase was extracted with EtOAc (3.times.). The combined
organic phases were washed with brine, dried over Na.sub.2SO.sub.4,
filtered, and the solvent evaporated. The crude oil was purified by
flash column chromatography (SiO.sub.2, 1.fwdarw.25% acetone in
hexanes) to afford the title compound (283 mg, 62%) as a colorless
oil; .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.30-7.23 (m, 2H),
7.05 (dd, J=8.5, 5.6 Hz, 2H), 6.98-6.80 (m, 49), 4.58 (t, J=5.2 Hz,
1H), 4.50 (d, J=11.4 Hz, 1H), 4.24 (d, J=11.4 Hz, 1H), 3.81 (s,
3H), 3.78-3.62 (m, 3H), 3.61-3.51 (m, 3H), 3.50-3.35 (m, 4H), 3.28
(s, 3H), 2.79 (dd, J=13.8, 5.4 Hz, 1H), 2.64 (dd, J=13.7, 8.2 Hz,
1H), 2.06-1.90 (m, 2H), 1.78-1.59 (m, 1H), 1.23 (t, J=7.0 Hz, 6H),
1.17 (d, J=6.4 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-118.16; ESIMS m/z 515 ([M+Na].sup.+).
Example 4, Step 6: Preparation of
1-((((2S,3S)-3-((S)-1-(2,2-diethoxyethoxy)-2-phenoxyethyl)heptan-2-yl)oxy-
)methyl)-4-methoxybenzene
##STR00030##
[0111] To a solution of
(2S,3S)-2-(2,2-diethoxyethoxy)-3-((S)-1-((4-methoxybenzyl)-oxy)ethyl)hept-
an-1-ol (1.00 g, 2.42 mmol) in toluene (15 mL) were added
bis(acctato-O)triphenylbismuth(V) (2.98 g, 5.33 mmol),
N-cyclohexyl-N-methylcyclohexanamine (1.14 mL, 5.33 mmol), and
diacetoxycopper (0.110 g, 0.606 mmol) at room temperature. The
reaction mixture was heated to and stirred at 50.degree. C. for 6 h
and then left at room temperature for 2 days (d). The reaction
mixture was filtered through a pad of Celite.RTM. and the filtrate
was concentrated. The crude residue was purified via flash column
chromatography (SiO.sub.2. 03-20% EtOAc in hexanes) to furnish the
title compound (1.12 g, 95%) as a colorless oil: IR (Thin Film)
2972, 2930, 2871, 1612, 1513 cm.sup.-1; .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.29-7.18 (m, 4H), 6.91 (tt, J=7.4, 1.1 Hz,
1H), 6.84-6.80 (m, 4H), 4.59 (dd, J=5.6, 4.9 Hz, 1H), 4.51 (d,
J=11.2 Hz, 1H), 4.34 (d, J=11.3 Hz, 1H), 4.09 (dd, J=10.3, 3.1 Hz,
1H), 4.03 (dd, J=10.3, 7.0 Hz, 1H), 3.88 (dt, J=6.9, 3.4 Hz, 1H),
3.77 (s, 3H), 3.74 (dd, J=10.5, 5.0 Hz, 1H), 3.72-3.63 (m, 3H),
3.60-3.49 (m, 3H), 1.88-1.79 (m, 1H), 1.49-1.38 (m, 2H), 1.36-1.25
(m, 4H), 1.24-1.14 (m, 9H), 0.89 (t, J=7.0 Hz, 31); ESIMS m/z 511
([M+Na].sup.+).
Example 5, Steps 1 and 2: Preparation methyl
2-((tert-butoxycarbonyl)amino)-4-(((3R,4S,5S)-4-(4-fluorobenzyl)-5-((4-me-
thoxybenzyl)oxy)-1-phenylhexan-3-yl)oxy)but-2-enoate
##STR00031##
[0112] Step 1
[0113] To a solution of
1-((2S,3R)-3-(2,2-diethoxyethoxy)-2-((S)-1-((4-methoxybenzyl)oxy)-ethyl)--
5-phenylpentyl)-4-fluorobenzene (759 mg, 1.20 mmol) in 2% aq.
CH.sub.3CN (12.0 mL) was added LiBF.sub.4 (123 mg, 1.32 mmol) in
one portion. The reaction vessel was fitted with a reflux condenser
and the mixture was heated to and stirred at 50.degree. C. for 2 h.
The reaction mixture was quenched with sat. aq. NaHCO.sub.3 and the
phases were separated. The aq. phase was extracted with DCM
(3.times.) and the combined organic phases were dried by passing
through a phase separator cartridge. The solvent was evaporated to
provide the desired aldehyde,
2-(((3R,4S,5S)-4-(4-fluorobenzyl)-5-((4-methoxybenzyl)oxy)-1-phenylhexan--
3-yl)oxy)acetaldehyde as a colorless oil.
Step 2
[0114] To a solution of
2-(((3R,4S,5S)-4-(4-fluorobenzyl)-5-((4-methoxybenzyl)oxy)-1-phenylhexan--
3-yl)oxy)acetaldehyde in DCM (13.5 mL) was added methyl
2-((tert-butoxycarbonyl)amino)-2-(dimethoxyphosphoryl)acetate (356
mg, 1.20 mmol) and the reaction mixture was cooled to 0.degree. C.
and treated with DBU (0.145 mL, 1.26 mmol). The reaction vessel was
sealed, left in the ice bath, and allowed to slowly warm to room
temperature over the weekend. The reaction mixture was quenched
with sat. aq. NH.sub.4Cl and then the phases were separated. The
sq. phase was extracted with DCM (3.times.) and the combined
organic phases were dried by passing through a phase separator
cartridge. The solvent was evaporated and the crude residue was
purified by flash column chromatography (SiO.sub.2, 1.fwdarw.15%
acetone in hexanes) to afford the title compound (566 mg, 74%) as a
predominately single alkene isomer: .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.26-7.19 (m, 4H), 7.19-7.11 (m, 1H), 7.09-6.98
(m, 4H), 6.96-6.83 (m, 4H), 6.49 (t, J=5.7 Hz, 2H), 4.50 (d, J=11.4
Hz, 1), 4.25 (d, J=11.4 Hz, 1H), 4.11 (d, J=5.8 Hz, 2H), 3.81 (s,
3H), 3.80 (d, J=2.3 Hz, 3H), 3.56 (dt, J=6.5, 3.2 Hz, 1H), 3.48
(dt, J=7.8, 3.8 Hz, 1H), 2.78-2.66 (m, 2H), 2.63 (dd, J=9.6, 5.3
Hz, 1H), 2.54 (ddd, J=13.8, 9.8, 6.6 Hz, 1H), 2.08 (tt, J=7.8, 3.9
Hz, 1H), 2.03-1.88 (m, 1H), 1.84-1.71 (m, 1H), 1.45 (s, 9H), 1.12
(d, J=6.3 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-117.92; ESIMS m/z 658 ([M+Na].sup.+).
Example 6, Step 1: Preparation of (S)-methyl
2-((Tert-butoxycarbonyl)amino)-4-(((3R,4S,5S)-4-(4-fluorobenzyl)-5-((4-me-
thoxybenzyl)oxy)-1-phenylhexan-3-yl)oxy)butanoate
##STR00032##
[0116] To a steel high pressure reactor was added methyl
2-((tert-butoxycarbonyl)amino)-4-(((3R,4S,5S)-4-(4-fluorobenzyl)-5-((4-me-
thoxybenzyl)oxy)-1-phenylhexan-3-yl)oxy)but-2-enoate (566 mg, 0.890
mmol) and MeOH (15 mL). The mixture was sparged with N.sub.2 for 20
min, treated with (S,S)-Et-DLPHOS-Rh (9.65 mg, 0.013 mmol), and
then the reactor was sealed, pressurized with H.sub.2 200 pounds
per square inch (psi), and vented. The process was repeated three
times, and then the reactor was pressurized to 200 psi with H.sub.2
and stirred vigorously over the weekend. The solvent was evaporated
and the resulting pale yellow oil was purified by flash column
chromatography (SiO.sub.2, 1.fwdarw.25% acetone in hexanes) to
afford the title compound (565 mg, 100%) as a colorless oil:
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.23 (t, J=8.0 Hz, 4H),
7.15 (t, J=7.3 Hz, 1H), 7.10-7.00 (m, 4H), 6.93 (t, J=8.7 Hz, 2H),
6.88 (d, J=8.6 Hz, 2H), 5.60 (d, J=7.8 Hz, 1H), 4.49 (d, J=11.3 Hz,
1H), 4.46-4.37 (m, 1H), 4.24 (d, J=11.4 Hz, 1H), 3.80 (s, 3H), 3.73
(s, 3H), 3.55 (dd, J=6.4, 4.7 Hz, 1H), 3.51-3.45 (m, 1H), 3.45-3.36
(m, 2H), 2.79-2.59 (m, 3H), 2.53 (ddd, J=13.7, 9.8, 6.6 Hz, 1H),
2.12-2.03 (m, 2H), 2.01-185 (m, 2H), 1.81-1.64 (m, 1H), 1.41 (s,
9H), 1.12 (d, J=6.2 Hz, 3H); .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta. -117.93; ESIMS m/z 660 ([M+Na].sup.+).
Example 6, Step 2: Preparation of(S)-methyl
2-((tert-butoxycarbonyl)amino)-4-(((3R,4S,5S)-4-(4-fluorobenzyl)-5-hydrox-
y-1-phenylhexan-3-yl)oxy)butanoate
##STR00033##
[0118] To a solution of (S)-methyl
2-((tert-butoxycarbonyl)amino)-4-(((3R,4S,5S)-4-(4-fluorobenzyl)-5-((4-me-
thoxybenzyl)oxy)-1-phenythexan-3-yl)oxy)butanoate (565 mg, 0.886
mmol) in DCM (3 mL) and water (0.3 mL) at 0.degree. C. was added
4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile (211
mg, 0.930 mmol) and the mixture was vigorously stirred for 45 min,
and then treated with 1 M aq. NaOH (930 .mu.L, 0.930 mmol) and
water (6 mL). The reaction was removed from the cold bath and the
phases were separated. The aqueous phase was extracted with DCM
(3.times.) and the combined organic phases were dried by passing
through a phase separator cartridge. The solvent was evaporated and
the resulting oil was purified by flash column chromatography
(SiO.sub.2, 1.fwdarw.20% acetone in hexanes) to afford the title
compound (440 mg, 96%) as a colorless oil: .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.25-7.20 (m, 2H), 7.19-7.08 (m, 3H), 7.08-7.03
(m, 2H), 6.96 (t, J=8.7 Hz, 2H), 5.46 (d, J=8.2 Hz, 1H), 4.45 (td,
J=9.1, 8.4, 5.2 Hz, 1H), 3.96-3.81 (m, 1H), 3.74 (s, 3H), 3.50
(ddd. J=9.3, 8.2, 4.3 Hz, 1H), 3.43 (dt. J=9.5, 5.1 Hz, 1H) 3.35
(td, J=6.2, 5.6, 3.1 Hz, 1H), 2.73-2.60 (m, 2H), 2.60-2.47 (m, 2H),
2.28-2.17 (m, 1H), 2.17-2.02 (m, 1H), 2.03-1.79 (m, 4H), 1.42 (s,
9H), 1.22 (d, J=6.4 Hz, 311); .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta. -117.51; ESIMS m/z 518 ([M+H].sup.+).
Example 6, Step 3: Preparation
of(S)-2-((ter-butoxycarbonyl)amino)-4-(((3R,4S,5S)-4-(4-fluorobenzyl)-5-h-
ydroxy-1-phenylhexan-3-yl)oxy)butanoic acid
##STR00034##
[0120] To a solution of (S)-methyl
2-(tert-butoxycarbonyl)amino)-4-(((3R,4S,5S)-4-(4-fluorobenzyl)-5-hydroxy-
-1-phenylhexan-3-yl)oxy)butanoate (430 mg, 0.831 mmol) in THF (5.5
mL) and water (2.8 mL) was added LiOH.H.sub.2O (105 mg, 2.49 mmol).
After 3 h, the reaction mixture was diluted with EtOAc (10 mL) and
washed with 0.2 M aq. HCl (10 mL) followed by brine. The organic
phase was dried over Na.sub.2SO.sub.4, filtered, and the solvent
was evaporated to afford the title compound (423 mg, 96%) as a
colorless oil: .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.25-7.17
(m, 2H), 7.16-7.13 (m, 1H), 7.10 (dd, J=8.5, 5.5 Hz, 2H), 7.05-7.00
(m, 2H), 6.95 (t, J=8.7 Hz, 2H), 5.55 (d, J=7.4 Hz, 1H), 4.42 (q,
J=6.4 Hz, 1H), 3.93 (p, J=6.2 Hz, 1H), 3.63-3.51 (m, 1H), 3.44 (dt,
J=9.7, 5.4 Hz, 1H), 3.36 (td, J=6.2, 3.0 Hz, 1H), 2.71-2.57 (m,
2H), 2.58-2.44 (m, 2H), 2.21-2.06 (m, 11H), 2.05-1.77 (m, 5H), 1.42
(a, 9H), 1.41-1.40 (m, 1H), 1.23 (d. J=6.2 Hz, 3H); .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -117.37; ESIMS m/z 504
([M+H].sup.+).
Example 7, Step 1: Preparation of tert-butyl
((2R,3S,4S,7S)-3-(4-fluorobenzyl)-4-methyl-6-oxo-2-phenethyl-1,5-dioxonan-
-7-yl)carbamate (Cmpd 97)
##STR00035##
[0122] To a solution of MNBA (572 mg, 1.66 mmol) and DMAP (608 mg,
4.98 mmol) in DCM (70 mL) was added a solution of
(S)-2-((tert-butoxycarbonyl)amino)-4-(((3R,4S,5S)-4-(4-fluorobenzyl)-5-hy-
droxy-1-phenylhexan-3-yl)oxy)butanoic acid (418 mg, 0.830 mmol) in
DCM (50 mL) dropwise over an 8 h period. Upon completion of the
addition, the reaction mixture was stirred overnight at room
temperature and then quenched with 0.2 M aq. HCl (100 mL). The
phases were separated and the organic phase was washed with half
sat. aq. NaHCO.sub.1 (100 mL) and dried by passing through a phase
separator cartridge. The solvent was evaporated and the crude
residue was purified by flash column chromatography (SiO.sub.2,
1.fwdarw.25% acetone in hexanes) to give the title compound (249
mg, 62%) as a white foam: See Table 2 for characterization
data.
Example 8, Step 1: Preparation of tert-butyl
((2S,3S,4S,7S)-3-butyl-2-(hydroxymethyl)-4-methyl-6-oxo-1,5-dioxonan-7-yl-
)carbamate
##STR00036##
[0124] To a solution of tert-butyl
((2S,3S,4S,7S)-2-((benzyloxy)methyl)-3-butyl-4-methy-6-oxo-1,5-dioxonan-7-
-yl)carbamate (110 mg, 0.245 mmol) in MeOH (5 mL) was added 10%
Pd/C (25 mg, 0.023 mmol). A balloon of H.sub.2 gas was fitted to
the reaction vessel. After 24 h of vigorous stirring, the reaction
mixture was filtered through a pad of Celite.RTM. and the pad was
washed with MeOH. The solvent was removed to afford the title
compound (85.5 mg, 97%) as a colorless oil; .sup.1H NMR (400 MHz,
CDCl) .delta. 5.18 (d, J=8.0 Hz, 1H), 5.15-5.06 (m, 1H), 4.25 (q,
J=8.4 Hz, 1H), 3.82-3.63 (m, 4H), 3.58-3.49 (m, 1H), 2.30 (dd,
J=15.2, 7.6 Hz, 1H), 2.05 (s, 1H), 1.93-1.80 (m, 1H), 1.81-1.68 (m,
1H), 1.68-1.54 (m, 2H), 1.44 (s, 9H), 1.34 (d, J=6.4 Hz, 3H),
1.32-1.20 (m, 4H), 0.89 (t, J=7.0 Hz, 3H); .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 172.45, 155.00, 81.06, 79.83, 74.51, 61.30,
59.17, 51.11, 40.27, 34.56, 28.34, 27.61, 27.29, 23.32, 19.21,
13.82; ESIMS m/z 360 ([M+H].sup.+).
Example 8, Step 2: Preparation of
((2S,3S,4S,7S)-7-((tert-butoxycarbonyl)amino)-3-butyl-4-methyl-6-oxo-1,5--
dioxonan-2-yl)methyl isobutyrate (Cmpd 105)
##STR00037##
[0126] To a solution of tert-butyl
((2S,3S,4S,7S)-3-butyl-2-(hydroxymethyl)-4-methyl-6-oxo-1,5-dioxonan-7-yl-
)carbamate (0.090 g, 0.250 mmol) in pyridine (1.0 mL) was added
DMAP (6.12 mg, 0.050 mmol) followed by isobutyryl chloride (0.052
mL, 0.501 mmol). The reaction mixture was stirred at room
temperature for 16 h and then quenched with sat, aq. NH.sub.4Cl (1
mL). The phases were separated and the aqueous phase was extracted
with DCM (3.times.4 mL). The combined extracts were dried by
passing through a phase separator and the solvent was evaporated.
The resulting residue was purified by flash column chromatography
(SiO.sub.2, 0.fwdarw.30% EtOAc in hexanes) to afford the title
compound (0.085 g, 79%) as a colorless oil: See Table 2 for
characterization data.
Example 9, Steps 1 and 2: Preparation of
N-((2R,3S,4S,7S)-3-(4-fluorobenzyl)-4-methyl-6-oxo-2-phenethyl-1,5-dioxon-
an-7-yl)-3-hydroxy-4-methoxypicolinamide (Cmpds 77 and 57)
##STR00038##
[0127] Step 1 (Cmpd 77)
[0128] To a solution of tert-butyl
((2R,3S,4S,7S)-3-(4-fluorobenzyl)-4-methyl-6-oxo-2-phenethyl-1,5-dioxonan-
-7-yl)carbamate (249 mg, 0.513 mmol) in DCM (3944 .mu.L) was added
a 4 M solution of HCl in dioxane (2.5 mL, 10.2 mmol). After 3 h at
room temperature, the solvent was evaporated under a stream of
N.sub.2 to provide the intermediate amine hydrochloride,
(2R,3S,4S,7S)-3-(4-fluorobenzyl)-4-methyl-6-oxo-2-phenethyl-1,5-dioxonan--
7-aminium chloride, as a pale yellow solid: See Table 2 for
characterization data.
Step 2 (Cmpd 57)
[0129] To a solution of
(2R,3S,4S,7S)-3-(4-fluorobenzyl)-4-methyl-6-oxo-2-phenethyl-1,5-dioxonan--
7-aminium chloride and 3-hydroxy-4-methoxypicolinic acid (95 mg,
0.56 mmol) in DCM (4 mL) were added
N-ethyl-N-isopropylpropan-2-amine (295 .mu.L, 1.69 mmol) and PYBOP
(294 mg, 0.564 mmol). The reaction vessel was sealed and the
mixture was stirred at room temperature for 4 h. The solvent was
evaporated and the crude oil was purified by flash column
chromatography (SiO.sub.2, 1.fwdarw.50% acetone in hexanes) to
afford the title compound (244 mg, 89%) as a white solid: See Table
2 for characterization data.
Example 10: Preparation of
((2-(((2R,3S,4S,7S)-3-(4-fluorobenzyl)-4-methyl-6-oxo-2-phenethyl-1,5-dio-
xonan-7-yl)carbamoyl)-4-methoxypyridin-3-yl)oxy)methyl acetate
(Cmpd 24)
##STR00039##
[0131] To a solution of
N-((2R,3S,4S,7S)-3-(4-fluorobenzyl)-4-methyl-6-oxo-2-phenethyl-1,5-dioxon-
an-7-yl)-3-hydroxy-4-methoxypicolinamide (73 mg, 0.14 mmol) and
K.sub.2CO.sub.3 (37.6 mg, 0.272 mmol) in acetone (1.4 mL) was added
bromomethyl acetate (18.7 .mu.L, 0.190 mmol) dropwise. The reaction
vessel was scaled and heated to 50.degree. C. and stirred for 4 h.
The mixture was filtered through a fritted filter rinsing with a
3:1 mixture of hexanes and acetone. The solvent was evaporated and
the crude residue was purified by flash column chromatography
(SiO.sub.2, 1.fwdarw.50% acetone in hexanes) to afford the title
compound (66.8 mg, 81%) as a white foam: See Table 2 for
characterization data.
Example 11: Preparation of
2-(((2R,3S,4S,7S)-3-(4-fluorobenzyl)-4-methyl-6-oxo-2-phenethyl-1,5-dioxo-
nan-7-yl)carbamoyl)-4-methoxypyridin-3-yl acetate (Cmpd 7)
##STR00040##
[0133] To a solution of
N-((2R,3S,4S,7S)-3-(4-fluorobenzyl)-4-methyl-6-oxo-2-phenethyl-1,5-dioxon-
an-7-yl)-3-hydroxy-4-methoxypicolinamide (73 mg, 0.14 mmol),
NEt.sub.3 (38 .mu.L, 0.272 mmol), and DMAP (3.3 mg, 0.027 mmol) in
DCM (1.4 mL) was added acetyl chloride (14.56 .mu.L, 0.204 mmol)
and the mixture was stirred for 3 h at mom temperature. The
reaction mixture was diluted with DCM, poured into sat. aq.
NH.sub.4Cl, and the phases were separated. The aq. phase was
extracted with DCM (3.times.) and the combined organics were dried
by passing through a phase separator cartridge. The solvent was
evaporated and the crude oil was purified by flash column
chromatography (SiO.sub.2, 1.fwdarw.50% acetone in hexanes) to
afford the title compound (77.9 mg, 99%) as a white foam: See Table
2 for characterization data.
Example 12: Preparation of
((2-(((2R,3S,4S,7S)-2,3-dibenzyl-4-methyl-6-oxo-1,5-dioxonan-7-yl)carbamo-
yl)-4-methoxypyridin-3-yl)oxy)methyl isobutyrate (Cmpd. 37)
##STR00041##
[0135] A 10 mL screw top vial was charged with
N-((2R,3S,4S,7S)-2,3-dibenzyl-4-methyl-6-oxo-1,5-dioxonan-7-yl)-3-hydroxy-
-4-methoxypicolinamide (90.0 mg, 0.178 mmol), sodium carbonate
(Na.sub.2CO.sub.3, 37.8 mg, 0.357 mmol), sodium iodide (NaI, 5.3
mg, 0.036 mmol), anhydrous acetone (1.78 mL) and chloromethyl
isobutyrate (39.0 mg, 0.285 mmol). The resulting mixture was heated
to 55.degree. C. and stirred at that temperature overnight. The
crude reaction mixture was cooled to room temperature, filtered
through a pad of Celite.RTM. rinsing with a 3:1 mixture of hexanes
and acetone, and the filtrate was concentrated. The resulting oil
was purified via column chromatography (SiO.sub.2, 1-50% acetone in
hexanes) to give the title compound (84.2 mg, 78%) as a white foam:
See Table 2 for characterization data.
Example 13: Preparation of
2-(((3R,4S,7S)-3-benzyl-4-methyl-6-oxo-1,5-dioxonan-7-yl)carbamoyl)-4-met-
hoxypyridin-3-yl 2-ethoxyacetate (Cmpd. 48) and
((2-(((3R,4S,7S)-3-benzyl-4-methyl-6-oxo-1,5-dioxonan-7-yl)carbamoyl)-4-m-
ethoxypyridin-3-yl)oxy)methyl 2-ethoxyacetate (Cmpd. 42)
##STR00042##
[0137] A 10 mL screw top vial was charged with
N-((3R,4S,7S)-3-benzyl-4-methyl-6-oxo-1,5-dioxonan-7-yl)-3-hydroxy-4-meth-
oxypicolinamide (83.0 mg, 0.182 mmol), Na.sub.2CO.sub.3 (41.9 mg,
0.396 mmol), NaI (5.93 mg, 0.040 mmol), anhydrous acetone (2.0 mL),
and chloromethyl 2-ethoxyacetate (40.2 .mu.l, 0.317 mmol), and the
resulting mixture was heated to 55.degree. C. and stirred at that
temperature overnight. The reaction mixture was cooled to room
temperature, treated with additional chloromethyl 2-ethoxyacetate
(13 .mu.L, 0.10 mmol), warmed to 55.degree. C., and stirred for 5
h. The crude reaction mixture was cooled to room temperature,
filtered through a plug of Celite.RTM. rinsing with a 3:1 mixture
of hexanes and acetone, and concentrated. The crude concentrate was
purified via column chromatography (SiO.sub.2, 1.fwdarw.50% acetone
in hexanes) to give the title compounds (42, 35.2 mg, 36% and 48,
53.5 mg, 51%) as white foams: See Table 2 for characterization
data.
Example A: Evaluation of Fungicidal Activity: Leaf Blotch of Wheat
(Mycosphaerella graminicola; Anamorph: Zymoseptoria tritici; Bayer
code SEPTTR)
[0138] Technical grades of materials were dissolved in acetone,
which were then mixed with nine volumes of water containing 110 ppm
Triton X-100. The fungicide solutions were applied onto wheat
seedlings using an automated booth sprayer to run-off. All sprayed
plants were allowed to air dry prior to further handling. All
fungicides were evaluated using the aforementioned method for their
activity vs. all target diseases, unless stated otherwise. Wheat
leaf blotch and brown rust activity were also evaluated using track
spray applications, in which case the fungicides were formulated as
EC formulations, containing 0.1% Trycol 5941 in the spray
solutions.
[0139] Wheat plants (variety Yuma) were grown from seed in a
greenhouse in 50% mineral soil/50% soil-less Metro mix until the
first leaf was fully emerged, with 7-10 seedlings per pot. These
plants were inoculated with an aqueous spore suspension of Septoria
tritici either prior to or after fungicide treatments. After
inoculation the plants were kept in 100% relative humidity (one day
in a dark dew chamber followed by two to three days in a lighted
dew chamber at 20.degree. C.) to permit spores to germinate and
infect the leaf. The plants were then transferred to a greenhouse
set at 20.degree. C. for disease to develop. When disease symptoms
were fully expressed on the 1.sup.st leaves of untreated plants,
infection levels were assessed on a scale of 0 to 100 percent
disease severity. Percent disease control was calculated using the
ratio of disease severity on treated plants relative to untreated
plants.
Example B: Evaluation of Fungicidal Activity: Wheat Brown Rust
(Puccinia triticina; Synonym: Puccinia recondita f. sp. tritici;
Bayer code PUCCRT)
[0140] Wheat plants (variety Yuma) were grown from seed in a
greenhouse in 50% mineral soil/50% soil-less Metro mix until the
first leaf was fully emerged, with 7-10 seedlings per pot. These
plants were inoculated with an aqueous spore suspension of Puccinia
triticina either prior to or after fungicide treatments. After
inoculation the plants were kept in a dark dew room at 22.degree.
C. with 100% relative humidity overnight to permit spores to
germinate and infect the leaf. The plants were then transferred to
a greenhouse set at 24.degree. C. for disease to develop. Fungicide
formulation, application and disease assessment followed the
procedures as described in the Example A.
Example C: Evaluation of Fungicidal Activity: Wheat Glume Blotch
(Leptosphaeria nodorum; Bayer code LEPTNO)
[0141] Wheat plants (variety Yuma) were grown from seed in a
greenhouse in 50% mineral soil/50% soil-less Metro mix until the
first leaf was fully emerged, with 7-10 seedlings per pot. These
plants were inoculated with an aqueous spore suspension of
Leptosphaeria nodorum 24 hr after fungicide treatments. After
inoculation the plants were kept in 100% relative humidity (one day
in a dark dew chamber followed by two days in a lighted dew chamber
at 20.degree. C.) to permit spores to germinate and infect the
leaf. The plants were then transferred to a greenhouse set at
20.degree. C. for disease to develop. Fungicide formulation,
application and disease assessment followed the procedures as
described in the Example A.
Example D: Evaluation of Fungicidal Activity: Apple Scab (Venturia
inaequalis: Bayer code VENTIN)
[0142] Apple seedlings (variety McIntosh) were grown in soil-less
Metro mix, with one plant per pot. Seedlings with two expanding
young leaves at the top (older leaves at bottom of the plants were
trimmed) were used in the test. Plants were inoculated with a spore
suspension of Venturia inaequalis 24 hr after fungicide treatment
and kept in a 22.degree. C. dew chamber with 100% relative humidity
for 48 hr. and then moved to a greenhouse set at 20.degree. C. for
disease to develop. Fungicide formulation, application and disease
assessment on the sprayed leaves followed the procedures as
described in the Example A.
Example E: Evaluation of Fungicidal Activity: Grape Powdery Mildew
(Uncinula necator; Bayer code UNCINE)
[0143] Grape seedlings (variety Carignane) were grown in soil-less
Metro mix, with one plant per pot, and used in the test when
approximately one month old. Plants were inoculated 24 hr after
fungicide treatment by shaking spores from infected leaves over
test plants. Plants were maintained in a greenhouse set at
20.degree. C. until disease was fully developed. Fungicide
formulation, application and disease assessment on the sprayed
leaves followed the procedures as described in the Example A.
Example F: Evaluation of Fungicidal Activity: Powdery Mildew of
Cucumber (Erysiphe cichoracearum; Bayer code ERYSCI)
[0144] Cucumber seedlings (variety Bush Pickle) were grown in
soil-less Metro mix, with one plant per pot, and used in the test
when 12 to 14 days old. Plants were inoculated with a spore
suspension 24 hr following fungicide treatments. After inoculation
the plants remained in the greenhouse set at 20.degree. C. until
disease was fully expressed. Fungicide formulation, application and
disease assessment on the sprayed leaves followed the procedures as
described in the Example A.
Example G: Evaluation of Fungicidal Activity: Leaf Spot of Sugar
Beets (Cercospora beticola; Bayer code CERCBE)
[0145] Sugar beet plants (variety HH88) were grown in soil-less
Metro mix and trimmed regularly to maintain a uniform plant size
prior to test. Plants were inoculated with a spore suspension 24 hr
after fungicide treatments. Inoculated plants were kept in a dew
chamber at 22.degree. C. for 48 hr then incubated in a greenhouse
set at 24.degree. C. under a clear plastic hood with bottom
ventilation until disease symptoms were fully expressed. Fungicide
formulation, application and disease assessment on the sprayed
leaves followed the procedures as described in the Example A.
Example H: Evaluation of Fungicidal Activity: Asian Soybean Rust
(Phakopsora pachyrhizi; Bayer code PHAKPA)
[0146] Technical grades of materials were dissolved in acetone,
which were then mixed with nine volumes of water containing 0.011%
Tween 20. The fungicide solutions were applied onto soybean
seedlings using an automated booth sprayer to run-off. All sprayed
plants were allowed to air dry prior to further handling.
[0147] Soybean plants (variety Williams 82) were grown in soil-less
Metro mix, with one plant per pot. Two weeks old seedlings were
used for testing. Plants were inoculated either 3 days prior to or
1 day after fungicide treatments. Plants were incubated for 24 h in
a dark dew room at 22.degree. C. and 100% relative humidity then
transferred to a growth room at 23.degree. C. for disease to
develop. Disease severity was assessed on the sprayed leaves.
Example 1: Evaluation of Fungicidal Activity: Wheat Powdery Mildew
(Blumeria graminis f. sp. tritici; Synonym: Erysiphe graminis f.
sp. tritici; Bayer code ERYSGT)
[0148] Wheat plants (variety Yuma) were grown from seed in a
greenhouse in 50% mineral soil/50% soil-less Metro mix until the
first leaf was fully emerged, with 7-10 seedlings per pot. These
plants were inoculated by dusting with infected stock plants 24 hr
after fungicide treatments. After inoculation the plants were kept
in a greenhouse set at 20.degree. C. for disease to develop.
Fungicide formulation, application and disease assessment on the
sprayed leaves followed the procedures as described in the Example
A.
Example J: Evaluation of Fungicidal Activity: Barley Powdery Mildew
(Blumeria graminis f. sp. hordei; Synonym: Erysiphe graminis f. sp.
hordei; Bayer code ERYSGH)
[0149] Barley seedlings (variety Harrington) were propagated in
soil-less Metro mix, with each pot having 8 to 12 plants, and used
in the test when first leaf was fully emerged. Test plants were
inoculated by dusting with infected stock plants 24 hr after
fungicide treatments. After inoculation the plants were kept in a
greenhouse set at 20.degree. C. for disease to develop. Fungicide
formulation, application and disease assessment on the sprayed
leaves followed the procedures as described in the Example A.
Example K: Evaluation of Fungicidal Activity: Barley Scald
(Rhyncosporium secalis; Bayer code RHYNSE)
[0150] Barley seedlings (variety Harrington) were propagated in
soil-less Metro mix, with each pot having 8 to 12 plants, and used
in the test when first leaf was fully emerged. Test plants were
inoculated by an aqueous spore suspension of Rhyncosporium secalis
24 hr after fungicide treatments. After inoculation the plants were
kept in a dew room at 20.degree. C. with 100% relative humidity for
48 hr. The plants were then transferred to a greenhouse set at
20.degree. C. for disease to develop. Fungicide formulation,
application and disease assessment on the sprayed leaves followed
the procedures as described in the Example A.
Example L: Evaluation of Fungicidal Activity; Rice Blast
(Magnaporthe grisea; Anamorph: Pyricularia oryzae; Bayer code
PYRIOR)
[0151] Rice seedlings (variety Japonica) were propagated in
soil-less Metro mix, with each pot having 8 to 14 plants, and used
in the test when 12 to 14 days old. Test plants were inoculated
with an aqueous spore suspension of Pyricularia oryzae 24 hr after
fungicide treatments. After inoculation the plants were kept in a
dew room at 22.degree. C. with 100% relative humidity for 48 hr to
permit spores to germinate and infect the leaf. The plants were
then transferred to a greenhouse set at 24.degree. C. for disease
to develop. Fungicide formulation, application and disease
assessment on the sprayed leaves followed the procedures as
described in the Example A.
Example M: Evaluation of Fungicidal Activity: Tomato Early Blight
(Alternaria solani; Bayer code ALTESO)
[0152] Tomato plants (variety Outdoor Girl) were propagated in
soil-less Metro mix, with each pot having one plant, and used when
12 to 14 days old. Test plants were inoculated with an aqueous
spore suspension of Alternaria solani 24 hr after fungicide
treatments. After inoculation the plants were kept in 100% relative
humidity (one day in a dark dew chamber followed by two to three
days in a lighted dew chamber at 20.degree. C.) to permit spores to
germinate and infect the leaf. The plants were then transferred to
a growth room at 22.degree. C. for disease to develop. Fungicide
formulation, application and disease assessment on the sprayed
leaves followed the procedures as described in the Example A.
Example N: Evaluation of Fungicidal Activity: Cucumber Anthracnose
(Glomerella lagenarium; Anamorph: Colletotrichum lagenarium; Bayer
code COLLLA)
[0153] Cucumber seedlings (variety Bush Pickle) were propagated in
soil-less Metro mix, with each pot having one plant, and used in
the test when 12 to 14 days old. Test plants were inoculated with
an aqueous spore suspension of Colletotrichum lagenarium 24 hr
after fungicide treatments. After inoculation the plants were kept
in a dew room at 22.degree. C. with 100% relative humidity for 48
hr to permit spores to germinate and infect the leaf. The plants
were then transferred to a growth room set at 22.degree. C. for
disease to develop. Fungicide formulation, application and disease
assessment on the sprayed leaves followed the procedures as
described in the Example A.
TABLE-US-00001 TABLE 1 Compound Structure, Appearance, and
Preparation Method Prepared According Compound to Number Structure
Example Appearance 1 ##STR00043## Example 11 White Foam 2
##STR00044## Example 11 White Foam 3 ##STR00045## Example 11 White
Foam 4 ##STR00046## Example 11 White Foam 5 ##STR00047## Example 11
White Foam 6 ##STR00048## Example 11 White Foam 7 ##STR00049##
Example 11 White Foam 8 ##STR00050## Example 11 White Foam 9
##STR00051## Example 11 White Powder 10 ##STR00052## Example 11
White Powder 11 ##STR00053## Example 11 White Powder 12
##STR00054## Example 11 White Powder 13 ##STR00055## Example 11
White Foam 14 ##STR00056## Example 11 Pale Yellow Solid 15
##STR00057## Example 11 Pale Yellow Oil 16 ##STR00058## Example 10
Off-White Solid 17 ##STR00059## Example 10 White Foam 18
##STR00060## Example 10 White Foam 19 ##STR00061## Example 10 White
Foam 20 ##STR00062## Example 10 White Foam 21 ##STR00063## Example
10 White Solid 22 ##STR00064## Example 10 White Foam 23
##STR00065## Example 10 White Foam 24 ##STR00066## Example 10 White
Foam 25 ##STR00067## Example 10 White Foam 26 ##STR00068## Example
10 White Powder 27 ##STR00069## Example 10 White Powder 28
##STR00070## Example 10 White Powder 29 ##STR00071## Example 10
White Powder 30 ##STR00072## Example 10 White Solid 31 ##STR00073##
Example 10 White Foam 32 ##STR00074## Example 10 Yellow Oil 33
##STR00075## Example 10 White Solid 34 ##STR00076## Example 10
Colorless Oil 35 ##STR00077## Example 10 Colorless Oil 36
##STR00078## Example 12 White Foam 37 ##STR00079## Example 12 White
Foam 38 ##STR00080## Example 12 White Foam 39 ##STR00081## Example
12 White Powder 40 ##STR00082## Example 12 White Powder 41
##STR00083## Example 12 White Solid 42 ##STR00084## Example 13
White Foam 43 ##STR00085## Example 13 White Foam 44 ##STR00086##
Example 13 White Foam 45 ##STR00087## Example 13 White Foam 46
##STR00088## Example 13 Colorless Oil 47 ##STR00089## Example 13
Colorless Oil 48 ##STR00090## Example 13 White Foam 49 ##STR00091##
Example 9, Step 2 White Foam 50 ##STR00092## Example 9, Step 2
White Solid 51 ##STR00093## Example 9, Step 2 White Foam 52
##STR00094## Example 9, Step 2 White Foam 53 ##STR00095## Example
9, Step 2 White Foam 54 ##STR00096## Example 9, Step 2 White Foam
55 ##STR00097## Example 9, Step 2 White Solid 56 ##STR00098##
Example 9, Step 2 White Solid 57 ##STR00099## Example 9, Step 2
White Solid 58 ##STR00100## Example 9, Step 2 White Foam 59
##STR00101## Example 9, Step 2 White Solid 60 ##STR00102## Example
9, Step 2 White Solid 61 ##STR00103## Example 9, Step 2 White
Powder 62 ##STR00104## Example 9, Step 2 White Solid 63
##STR00105## Example 9, Step 2 Sticky White Solid 64 ##STR00106##
Example 9, Step 2 White Solid 65 ##STR00107## Example 9, Step 2
White Foam 66 ##STR00108## Example 9, Step 2 Colorless oil 67
##STR00109## Example 9, Step 2 Colorless Solid 68 ##STR00110##
Example 9, Step 2 White Solid 69 ##STR00111## Example 9, Step 1
White Solid 70 ##STR00112## Example 9, Step 1 White Solid 71
##STR00113## Example 9, Step 1 White Solid 72 ##STR00114## Example
9, Step 1 White Solid 73 ##STR00115## Example 9, Step 1 White Foam
74 ##STR00116## Example 9, Step 1 White Solid 75 ##STR00117##
Example 9, Step 1 White Solid 76 ##STR00118## Example 9, Step 1
White Solid 77 ##STR00119## Example 9, Step 1 White Solid 78
##STR00120## Example 9, Step 1 White Solid 79 ##STR00121## Example
9, Step 1 White Powder 80 ##STR00122## Example 9, Step 1 White
Solid 81 ##STR00123## Example 9, Step 1 White Solid 82 ##STR00124##
Example 9, Step 1 White Solid 83 ##STR00125## Example 9, Step 1
White Solid 84 ##STR00126## Example 9, Step 1 White Solid 85
##STR00127## Example 9, Step 1 White Solid 86 ##STR00128## Example
9, Step 1 White Solid 87 ##STR00129## Example 9, Step 1 White Solid
88 ##STR00130## Example 9, Step 1 Colorless Solid 89 ##STR00131##
Example 1 Steps 1, 3; Example 2, Step 5; Example 3, Steps 1, 2, 3;
Example 6 Steps 1, 2, 3; Example 7, Step 1 Pale Yellow Oil 90
##STR00132## Example 1 Steps 1, 3; Example 2, Steps 1, 2, 3, 4;
Example 4, Step 1; Example 5, Steps 1, 2; Example 6, Colorless Oil
Steps 1, 2, 3; Example 7, Step 1 91 ##STR00133## Example 1, Steps
1, 3; Example 2, Steps 1, 2; Example 4 Steps 1, 2; Example 5, Steps
1, 2; Example 6, Steps 1, 2, 3; Example 7, Step 1 White Foam 92
##STR00134## Example 1, Steps 1, 3; Example 2, Steps 1, 2, 3, 4;
Example 3, Steps 1, 2, 3; Example 6, Steps 1, 2, 3; Example 7, Step
1 White Foam 93 ##STR00135## Example 1 Steps 1, 3; Example 2, Steps
1, 2; Example 4, Steps 1, 3, 5; Example 5, Steps 1, 2; Example 6,
Steps 1, 2, 3; Example 7, Step 1 White Foam 94 ##STR00136## Example
1, Steps 1, 3; Example 2, Step 5; Example 3, Steps 1, 2, 3; Example
6, Steps 1, 2, 3; Example 7, Step 1 Pale Yellow Oil 95 ##STR00137##
Example 1, Steps 1, 3; Example 2, Steps 1, 2; Example 4, Step 1;
Example 5 Steps 1, 2; Example 6, Steps 1, 2, 3; White Foam Example
7, Step 1 96 ##STR00138## Example 1, Steps 1, 3; Example 2, Steps
1, 2; Example 4, Steps 1, 2; Example 5, Steps 1, 2; Example 6,
Steps 1, 2, 3; Example 7, Step 1 White Foam 97 ##STR00139## Example
1, Steps 1, 3; Example 2, Steps 1, 2; Example 4, Steps 1, 2;
Example 5, Steps 1, 2; Example 6, Steps 1, 2, 3; Example 7, Step 1
White Foam 98 ##STR00140## Example 1, Steps 1, 3; Example 2, Steps
1, 2; Example 4, Steps 1,3, 5; Example 5, Steps 1, 2; Example 6,
Steps 1, 2, 3; Example 7, Step 1 White Foam 99 ##STR00141## Example
1, Steps 1, 2, 3; Example 2, Steps 1, 2; Example 4, Steps 1, 2;
Example 5, Steps 1, 2; Example 6, Steps 1, 2, 3; Example 7, Step 1
Sticky White Solid 100 ##STR00142## Example 1, Steps 1, 2, 3;
Example 2, Steps 1, 2; Example 4, Steps 1, 2; Example 5, Steps 1,
2; Example 6, Steps 1, 2, 3; Example 7, Step 1 White Powder 101
##STR00143## Example 1, Step 1; Example 2, Step 5b; Example 3,
Steps 1b, 2, 3; Example 6, Steps 1, 3; Example 7, Step 1 Sticky
Solid 102 ##STR00144## Example 1, Steps 1, 2, 3; Example 2, Steps
1, 2, 3, 4; Example 3, Steps 1a, 2, 3; Example 6, Steps 1, 2, 3;
Example 7, Step 1 White Solid 103 ##STR00145## Example 1, Steps 1,
2; Example 2, Step 5b; Example 3, Steps 1b, 2, 3; Example 6, Steps
1, 3; Example 7, White Solid Step 1 104 ##STR00146## Example 1,
Steps 1, 2, 3; Example 2, Steps 1, 2 ; Example 4, Steps 1, 2;
Example 5, Steps 1, 2; Example 6, Steps 1, 2, 3; Colorless Oil
Example 7,
Step 1 105 ##STR00147## Example 1, Steps 1, 2, 3; Example 2, Steps
1, 2; Example 4, Steps 1, 4, 5; Example 5, Steps 1, 2; Example 6,
Steps 1, 2, 3; Example 7, Step 1; Colorless Oil Example 8, Steps 1,
2 106 ##STR00148## Example 1, Steps 1, 2, 3; Example 2, Step 5;
Example 3, Steps 1, 2, 3; Example 6, Steps 1, 2, 3; Example 7, Step
1 White Solid 107 ##STR00149## Example 1, Steps 1, 2, 3; Example 2,
Steps 1, 2, 3, 4; Example 4, Step 1; Example 5, Steps 1, 2; Example
6, Colorless Oil Steps, 1, 2, 3; Example 7, Step 1 108 ##STR00150##
Example 1, Steps 1, 2, 3; Example 2, Steps 1, 2, 3, 4; Example 4,
Steps 1, 4, 6; Example 5, Steps 1, 2; Example 6, Steps 1, 2, 3;
Example 7, Step 1 Colorless Oil
TABLE-US-00002 TABLE 2 Analytical Data Compound MP IR NMR Number
(.degree. C.) (cm.sup.-1) MASS (.sup.1H, .sup.13C, .sup.19F) 1 --
(Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.77 (d, J
= 7.3 Film) (m/z) Hz, 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.31-7.26
3378, [M + H].sup.+ (m, 2H), 7.26-7.22 (m, 2H), 7.24-7.15 (m, 3025,
calcd for 1H), 7.00 (d, J = 5.4 Hz, 1H) 5.18 (qd, J = 2930,
C.sub.24H.sub.29N.sub.2O.sub.7, 6.6, 3.6 Hz, 1H), 4.67 (td, J =
7.8, 5.4 Hz, 1H), 1770, 457.1969; 3.92 (ddd, J = 11.3, 7.4, 2.6 Hz,
1H), 3.89 (s, 1740, found, 3H), 3.63 (dd, J = 10.7, 4.2 Hz, 1H),
3.49 (dd, 1677, 457.1978 J = 10.8, 2.6 Hz, 1H), 3.43 (ddd, J =
11.3, 7.6, 1506 2.5 Hz, 1H), 2.87 (dd, J = 13.5, 7.7 Hz, 1H), 2.77
(dd, J = 13.5, 8.4 Hz, 1H), 2.51-2.41 (m, 1H), 2.40 (s, 3H), 1.88
(dtd, J = 14.5, 7.9, 2.8 Hz, 1H) 1.83-1.76 (m, 1H), 1.24 (d, J =
6.6 Hz, 3H) 2 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.62 (d, J = 8.2 Film) (m/z) Hz, 1H), 8.32 (d, J = 5.4 Hz,
1H), 7.34-7.25 3379, [M + H].sup.+ (m, 2H), 7.23-7.12 (m, 3H), 6.99
(d, J = 5.5 2934, calcd for Hz, 1H), 5.17 (dq, J = 9.5, 6.5 Hz,
1H), 4.60 2871, C.sub.28H.sub.37N.sub.2O.sub.7, (dt, J = 10.0, 7.7
Hz, 1H), 3.88 (s, 3H), 3.61 1770, 513.2595; (dd, J = 11.1, 9.4 Hz,
1H), 3.55-3.43 (m, 1743, found, 2H), 2.61 (dd, J = 15.8, 3.5 Hz,
1H), 2.51 (dd, 1676, 513.2609 J = 15.8, 6.6 Hz, 1H), 2.39 (s, 3H),
2.21 1506 (dddd, J = 13.3, 10.0, 6.6, 3.4 Hz, 1H), 1.75- 1.61 (m,
1H), 1.61-1.53 (m, 2H), 1.49-1.39 (m, 1H), 1.27 (d, J = 6.5 Hz,
3H), 1.37-1.19 (m, 3H), 0.87 (t, J = 7.1 Hz, 3H), 2.44-2.32 (m, 1H)
3 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.57
(d, J = 7.9 Film) (m/z) Hz, 1H), 8.29 (d, J = 5.4 Hz, 1H),
7.35-7.24 3378, [M + H].sup.+ (m, 3H) 7.26-7.20 (m, 4H) 7.19-7.15
(m, 2936, calcd for 3H), 6.96 (d, J = 5.5 Hz, 1H), 5.21 (dq, J =
1770, C.sub.31H.sub.35N.sub.2O.sub.7, 9.6, 6.5 Hz, 1H), 4.61 (ddd,
J = 9.6, 8.1, 7.2 1744, 547.2439; Hz, 1H), 3.99 (td, J = 10.6, 2.5
Hz, 1H), 3.86 1677, found, (s, 3H), 3.62 (t, J = 9.9 Hz, 1H), 3.41
(ddd, J = 1507 547.2448 9.6, 4.7, 2.0 Hz, 1H), 3.00 (dd, J = 15.7,
2.5 Hz, 1H) 2.85 (dd, J = 15.7, 10.9 Hz, 1H), 2.75 (dd, J = 15.9,
3.8 Hz, 1H), 2.65 (dd, J = 15.8, 6.2 Hz, 1H), 2.37 (s, 3H),
2.42-2.32 (m, 1H), 2.27 (ddd, J = 14.2, 7.3, 4.9 Hz, 1H), 1.64-
1.52 (m, 1H) 1.35 (d, J = 6.5 Hz, 3H) 4 -- (Thin HRMS-ESI .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 8.63 (d, J = 8.1 Film) (m/z) Hz,
1H), 8.33 (d, J = 5.4 Hz, 1H), 7.33-7.24 3377, [M + H].sup.+ (m,
2H), 7.23-7.16 (m, 3H), 6.99 (d, J = 5.5 2937, calcd for Hz, 1H),
5.15 (dq, J = 9.5, 6.5 Hz, 1H), 4.61 2876,
C.sub.27H.sub.35N.sub.2O.sub.8, (dt, J = 10.0, 7.7 Hz, 1H), 3.90
(s, 3H), 3.73- 1770, 515.2388; 3.60 (m, 2H), 3.53-3.47 (m, 1H),
3.47-3.33 1744, found, (m, 2H), 3.31 (s, 3H), 2.61 (dd, J = 15.9,
3.5 1676, 515.2390 Hz, 1H), 2.51 (dd, J = 15.9, 6.4 Hz, 1H), 2.44-
1507 2.40 (m, 1H), 2.69 (s, 3H), 2.26 (tdd, J = 10.0, 6.3, 3.4 Hz,
1H), 2.02-1.80 (m, 2H), 1.75-1.66 (m, 1H), 1.28 (d, J = 6.5 Hz, 3H)
5 -- -- HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
8.81-8.71 (m, (m/z) 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.20 (dd, J = [M
+ H].sup.+ 8.5, 5.5 Hz, 2H, 7.01 (d, J = 5.5 Hz, 1H), 6.97 calcd
for (t, J = 8.7 Hz, 2H), 5.16 (qd, J = 6.7, 3.2 Hz,
C.sub.24H.sub.28FN.sub.2O.sub.7, 1H), 4.67 (td, J = 7.8, 5.3 Hz,
1H), 3.98-3.91 475.1875; (m, 1H), 3.90 (s, 3H), 3.62 (dd, J = 10.7,
3.9 found, Hz, 1H), 3.49 (dd, J = 10.7, 2.4 Hz, 1H), 3.42 475.1887
(ddd, J = 11.2, 7.6, 2.5 Hz, 1H), 2.85 (dd, J = 13.6, 7.9 Hz, 1H),
2.77 (dd, J = 13.6, 8.4 Hz, 1H), 2.52-2.41 (m, 1H), 2.40 (s, 3H),
1.88 (dtd, J = 15.8, 9.3, 8.6, 3.5 Hz, 1H) 1.72 (ttd, J = 7.8, 3.7,
2.3 Hz, 1H), 1.24 (d, J = 6.7 Hz, 3H) .sup.19F NMR (376 MHz,
CDCl.sub.3) .delta. -117.23 6 -- -- HRMS-ESI .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.62 (d, J = 8.9 (m/z) Hz, 1H), 8.33 (d, J =
5.4 Hz, 1H), 7.13 (dd, J = [M + H].sup.+ 8.5, 5.4 Hz, 2H),
7.03-6.95 (m, 3H), 5.15 calcd for (dq, J = 9.4, 6.5 Hz, 1H), 4.60
(dt, J = 10.0, C.sub.28H.sub.36FN.sub.2O.sub.7, 7.7 Hz, 1H), 3.90
(s, 3H), 3.61 (dd, J = 11.1, 531.2501; 9.4 Hz, 1H), 3.55-3.40 (m,
2H), 2.58 (dd, J = found, 15.9, 3.5 Hz, 1H), 2.50 (dd, J = 15.8,
6.5 Hz, 531.2501 1H), 2.39 (s, 3H), 2.44-2.32 (m, 1H), 2.21- 2.09
(m, 1H), 1.74-1.62 (m, 1H), 1.62-1.48 (m, 2H), 1.38-1.19 (m, 4H),
1.26 (d, J = 6.4 Hz, 3H), 0.88 (t, J = 7.0 Hz, 3H) .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -116.89 7 -- -- HRMS-ESI .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 8.64 (d, J = 7.8 (m/z) Hz, 1H), 8.33
(d, J = 5.4 Hz, 1H), 7.31-7.23 [M + H].sup.+ (m, 2H), 7.19 (t, J =
7.3 Hz, 1H), 7.13 (d, J = calcd for 8.0 Hz, 2H), 7.03-6.97 (m, 3H),
6.91 (t, J = C.sub.32H.sub.36FN.sub.2O.sub.7, 8.6 Hz, 2H), 5.13
(dq, J = 9.5, 6.4 Hz, 1H), 579.2501; 4.62 (dt, J = 10.1, 7.7 Hz,
1H), 3.89 (s, 3H), found, 3.71-3.57 (m, 2H), 3.52 (td, J = 10.7,
2.3 Hz, 579.2495 1H), 2.78 (ddd, J = 13.7, 8.9, 4.6 Hz, 1H),
2.62-2.49 (m, 2H), 2.51-2.38 (m, 2H), 2.39 (s, 3H), 2.22-2.10 (m,
1H), 2.01-1.66 (m, 3H), 1.27 (d, J = 6.5 Hz, 3H) .sup.19F NMR (376
MHz, CDCl.sub.3) .delta. -116.76 8 -- -- HRMS-ESI .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.63 (t, J = 4.8 (m/z) Hz, 1H), 8.33 (d, J
= 5.4 Hz, 1H), 7.15 (dd, J = [M + H].sup.+ 8.5, 5.4 Hz, 2H),
7.02-6.92 (m, 3H), 5.13 calcd for (dq, J = 9.5, 6.5 Hz, 1H), 4.61
(dt, J = 10.0, C.sub.27H.sub.34FN.sub.2O.sub.8, 7.7 Hz, 1H), 3.89
(s, 3H), 3.74-3.58 (m, 2H), 533.2294; 3.54-3.35 (m, 3H), 3.31 (s,
3H), 2.58 (dd, J = found, 15.8, 3.7 Hz, 1H), 2.50 (dd, J = 15.9,
6.3 Hz, 533.2290 1H), 2.45-2.34 (m, 1H), 2.39 (s, 3H), 2.27- 2.13
(m, 1H), 1.99-1.80 (m, 2H), 1.78-1.67 (m, 1H), 1.27 (d, J = 6.5 Hz,
3H) .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -116.85 9 70-74 --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.64 (d, J = 8.3
(m/z) Hz, 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.33-7.24 [M + H].sup.+
(m, 2H), 7.23-7.14 (m, 3H), 7.00 (d, J = 5.4 calcd for Hz, 1H),
5.08 (dq, J = 9.6, 6.4 Hz, 1H), 4.68-
C.sub.30H.sub.41N.sub.2O.sub.7, 4.56 (m, 1H), 3.90 (s, 3H),
3.66-3.49 (m, 541.2908; 3H), 2.82 (ddd, J = 13.6, 8.9, 4.7 Hz, 1H),
found, 2.64-2.52 (m, 1H), 2.47-2.36 (m, 4H), 1.90- 541.2910 1.66
(m, 4H), 1.36-1.18 (m, 6H), 1.01- 0.89 (m, 2H), 0.82 (d, J = 6.6
Hz, 3H), 0.79 (d, J = 6.6 Hz, 3H) 10 76-80 -- HRMS-ESI .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 8.63 (d, J = 8.3 (m/z) Hz, 1H), 8.34
(d, J = 5.4 Hz, 1H), 7.18-7.10 [M + H].sup.+ (m, 2H), 7.04-6.92 (m,
3H), 5.07 (dq, J = calcd for 9.6, 6.4 Hz, 1H), 4.61 (app dt, J =
10.2, 7.8 C.sub.30H.sub.40FN.sub.2O.sub.7, Hz, 1H), 3.90 (s, 3H),
3.66-3.47 (m, 3H), 559.2814 2.78 (ddd, J = 13.5, 8.4, 4.4 Hz, 1H),
2.62- found, 2.50 (m, 1H), 2.47-2.34 (m, 4H), 1.89-1.69 559.2825
(m, 4H), 1.39-1.27 (m, 4H), 1.25-1.13 (m, 2H), 1.02-0.84 (m, 2H),
0.82 (d, J = 6.6 Hz, 3H), 0.79 (d, J = 6.6 Hz, 3H) 11 77-82 --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.73 (d, J = 7.2
(m/z) Hz, 1H), 8.34 (d, J = 5.4 Hz 1H), 7.45-7.14 [M + H].sup.+ (m,
9H), 6.99 (d, J = 5.5 Hz, 1H), 4.92 (qd, J = calcd for 6.6, 4.3 Hz,
1H), 4.59 (app td, J = 7.6, 5.3 Hz, C.sub.30H.sub.33N.sub.2O.sub.7,
1H), 3.89 (s, 3H), 3.80 (ddd, J = 10.8, 7.7, 2.7 533.2282; Hz, 1H),
3.37-3.20 (m, 3H), 2.90 (dd, J = found, 13.6, 6.0 Hz, 1H), 2.78
(dd, J = 13.6, 9.4 Hz, 533.2288 1H), 2.46-2.34 (m, 4H), 1.87-1.74
(m, 1H), 1.42-1.32 (m, 1H), 0.90 (d, J = 6.6 Hz, 3H) 12 83-88 --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.57 (d, J = 8.0
(m/z) Hz, 1H), 8.30 (d, J = 5.4 Hz, 1H), 7.33-7.23 [M + H].sup.+
(m, 4H), 7.23-7.15 (m, 1H), 6.97 (d, J = 5.5 calcd for Hz, 1H),
5.14 (dq, J = 9.7, 6.4 Hz, 1H), 4.60
C.sub.29H.sub.39N.sub.2O.sub.7, (ddd, J = 9.5, 8.2, 7.3 Hz, 1H),
4.02 (app td, J = 527.2752; 10.5, 3.0 Hz, 1H), 3.87 (s, 3H), 3.57
(app t, J = found, 9.9 Hz, 1H), 3.42-3.33 (m, 1H), 2.92 (dd, J =
527.2756 15.5, 3.1 Hz, 1H), 2.82 (dd, J = 15.5, 10.4 Hz, 1H), 2.38
(s, 3H), 2.33-2.21 (m, 1H), 1.99-1.87 (m, 1H), 1.65-1.51 (m, 1H),
1.50- 1.32 (m, 6H), 1.30-1.11 (m, 2H), 0.89 (d, J = 6.6 Hz, 3H),
0.87 (d, J = 6.6 Hz, 3H) 13 -- -- HRMS-ESI .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.64 (d, J = 8.3 (m/z) Hz, 1H), 8.34 (d, J =
5.4 Hz, 1H), 7.33-7.25 [M + H].sup.+ (m, 2H) 7.23-7.15 (m, 3H),
7.00 (d, J = 5.5 calcd for Hz, 1H), 5.09 (dq, J = 9.7, 6.4 Hz, 1H),
4.62 C.sub.29H.sub.38N.sub.2O.sub.7, (dt, J = 10.2, 7.8 Hz, 1H),
3.90 (s, 3H), 3.66- 527.2752; 3.50 (m, 3H), 2.82 (ddd, J = 13.9,
9.0, 4.9 Hz, found, 1H), 2.58 (dt, J = 13.9, 8.3 Hz, 1H), 2.47-
527.2740 2.41 (m, 1H), 2.40 (s, 3H), 1.92-1.67 (m, 4H) 1.30 (d, J =
6.4 Hz, 3H), 1.21 (m, 4H), 1.13-1.01 (m, 2H), 0.83 (t, J = 7.2 Hz,
3H) .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 172.01, 168.91,
162.52, 159.37, 146.78, 141.84, 141.51, 137.42, 128.43, 128.40,
125.93, 109.76, 79.40, 74.94, 57.66, 56.28, 49.87, 43.36, 34.23,
32.23, 31.45, 27.84, 27.47, 23.32, 20.77, 19.36, 13.81 14 -- (Thin
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.63 (d, J = 8.2
Film) (m/z) Hz, 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.00 (d, J = 3380,
[M].sup.+ 5.5 Hz, 1H), 5.17-5.04 (m, 1H), 4.66-4.55 2934, calcd for
(m, 1H), 3.90 (s, 3H), 3.61-3.51 (m, 1H), 1771,
C.sub.23H.sub.34N.sub.2O.sub.7, 3.50-3.41 (m, 2H), 2.44-2.32 (m,
1H), 2.39 1676, 450.2366; (s, 3H), 1.84-1.40 (m, 4H), 1.31 (d, J =
6.5 1507, found, Hz, 3H), 1.29-1.09 (m, 6H), 0.97 (t, J = 7.3 1369,
450.2371 Hz, 3H), 0.88 (t, J = 6.9 Hz, 3H) 1192 .sup.13C NMR (101
MHz, CDCl.sub.3) .delta. 172.00, 168.86, 162.48, 159.34, 146.77,
141.48, 137.38, 109.74, 82.06, 74.97, 57.42, 56.26, 49.88, 43.62,
34.24, 27.96, 27.77, 23.37, 22.69, 20.73, 19.35, 13.85, 10.83 15 --
(Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.62 (d, J
= 8.1 Film) (m/z) Hz, 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.34-7.25
3380, [M].sup.+ (m, 2H), 7.01-6.90 (m, 4H), 5.23-5.13 (m, 2935,
calcd for 1H), 4.70-4.59 (m, 1H), 4.20-4.06 (m, 2H), 1742,
C.sub.28H.sub.36N.sub.2O.sub.8, 4.05-3.96 (m, 1H), 3.91-3.81 (m,
1H), 3.89 1676, 528.2472; (s, 3H), 3.63-3.53 (m, 1H), 2.39 (s, 3H),
2.37- 1506, found, 2.30 (m, 1H), 2.28-2.17 (m, 1H), 1.79- 1369,
528.2470 1.65 (m, 1H), 1.38 (d, J = 6.4 Hz, 3H), 1.37- 1192 1.14
(m, 6H), 0.88 (t, J = 6.8 Hz, 3H) .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 171.97 168.88, 162.48, 159.38, 158.37, 146.78,
141.46, 137.41, 129.53, 121.15, 114.54, 109.80, 101.44, 78.33,
74.64, 67.40, 60.50, 56.28, 50.07, 40.01, 34.37, 30.07, 27.54,
27.25, 23.34, 20.75, 19.27, 13.85 16 -- (Thin HRMS-ESI .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 8.56 (d, J = 7.4 Film) (m/z) Hz, 1H),
8.30 (d, J = 5.3 Hz, 1H), 7.31-7.26 3349, [M + H].sup.+ (m, 2H),
7.26-7.22 (m, 2H), 7.22-7.17 (m, 2989, calcd for 1H), 6.96 (d, J =
5.4 Hz, 1H), 5.80-5.69 (m, 2892, C.sub.25H.sub.31N.sub.2O.sub.8,
2H), 5.19 (qd, J = 6.6, 3.7 Hz, 1H), 4.70 (td, J = 1755, 487.2075;
7.7, 5.4 Hz, 1H), 3.97-3.92 (m, 1H), 3.91 1745, found, (s, 3H),
3.63 (dd, J = 10.7, 4.2 Hz, 1H), 3.50 1730, 487.2084 (dd, J = 10.8,
2.6 Hz, 1H), 3.45 (ddd, J = 11.3, 1684, 7.6, 2.5 Hz, 1H), 2.87 (dd,
J = 13.5, 7.7 Hz, 1505 1H), 2.77 (dd, J = 13.5, 8.5 Hz, 1H), 2.49
(dddd, J = 14.4, 7.7, 5.4, 2.5 Hz, 1H), 2.07 (s, 3H), 1.99-1.84 (m,
1H), 1.82 (ttd, J = 7.9, 4.0, 2.5 Hz, 1H), 1.25 (d, J = 6.6 Hz, 3H)
17 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.40
(d, J = 8.1 Film) (m/z) Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 7.30 (t,
J = 3378, [M + H].sup.+ 7.3 Hz, 2H), 7.24-7.13 (m, 3H), 6.94 (d, J
= 2933, calcd for 5.4 Hz, 1H), 5.77-5.68 (m, 2H), 5.18 (dq, J =
2873, C.sub.28H.sub.37N.sub.2O.sub.8, 9.4, 6.5 Hz, 1H), 4.63 (dt, J
= 10.1, 7.6 Hz, 1747, 529.2544; 1H), 3.91 (s, 3H), 3.70-3.58 (m,
1H), 3.57- 1675, found, 3.43 (m, 2H), 2.63 (dd, J = 15.6, 3.5 Hz,
1H), 1499 529.2551 2.51 (dd, J = 15.8, 6.7 Hz, 1H), 2.42 (ddd, J =
14.0, 7.5, 3.7 Hz, 1H), 2.27-2.17 (m, 1H), 2.06 (s, 3H), 1.76-1.59
(m, 3H), 1.59-1.41 (m, 2H), 1.28 (d, J = 6.5 Hz, 3H) 0.89 (t, J =
7.1 Hz, 3H) 18 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.40 (d, J = 8.1
Film) (m/z) Hz, 1H), 8.28 (d, J = 5.4 Hz, 1H), 7.32-7.26 3379, [M +
H].sup.+ (m, 2H), 7.23-7.14 (m, 3H), 6.95 (d, J = 5.4 2934, calcd
for Hz, 1H), 5.81-5.66 (m, 2H), 5.18 (dq, J = 2872,
C.sub.29H.sub.39N.sub.2O.sub.8, 9.5, 6.5 Hz, 1H), 4.63 (dt, J =
10.1, 7.7 Hz, 1749, 543.2701; 1H), 3.90 (s, 3H), 3.69-3.60 (m, 1H),
3.56- 1676, found, 3.45 (m, 2H), 2.62 (dd, J = 15.8, 3.4 Hz, 1H),
1504 543.2709 2.52 (dd, J = 15.8, 6.6 Hz, 1H), 2.42 (ddd, J = 14.0,
7.5, 3.7 Hz, 1H), 2.23 (dddd, J = 12.7, 10.0, 6.6, 3.4 Hz, 1H),
2.06 (s, 3H), 1.77- 1.64 (m, 1H), 1.64-1.53 (m, 2H), 1.45 (dddd, J
= 16.4, 11.3, 5.3, 2.3 Hz, 1H), 1.35-1.20 (m, 3H), 1.29 (d, J = 6.5
Hz, 3H), 0.88 (t, J = 7.0 Hz, 3H) 19 -- (Thin HRMS-ESI .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 8.35 (d, J = 7.9 Film) (m/z) Hz, 1H),
8.25 (d, J = 5.4 Hz, 1H), 7.34-7.26 3377, [M + H].sup.+ (m, 3H),
7.28-7.21 (m, 4H), 7.18 (d, J = 7.1 3026, calcd for Hz, 3H), 6.92
(d, J = 5.4 Hz, 1H), 5.76-5.63 2936,
C.sub.32H.sub.37N.sub.2O.sub.8, (m, 2H), 5.22 (dq, J = 9.6, 6.5 Hz,
1H), 4.64 1747, 577.2544; (dt, J = 9.6, 7.5 Hz, 1H), 4.00 (td, J =
10.6, 2.5 1674, found, Hz, 1H), 3.88 (s, 3H), 3.66 (t, J = 10.0 Hz,
1497 577.2552 1H), 3.43 (ddd, J = 9.5, 4.6, 2.2 Hz, 1H), 3.01 (dd,
J = 15.8, 2.6 Hz, 1H), 2.87 (dd, J = 15.7, 10.9 Hz, 1H), 2.76 (dd,
J = 15.9, 3.8 Hz, 1H), 2.66 (dd, J = 15.8, 6.2 Hz, 1H), 2.39 (tdd,
J = 10.0, 6.3, 3.9 Hz, 1H), 2.30 (ddd, J = 14.6, 7.4, 4.4 Hz, 1H),
2.04 (s, 3H), 1.66-1.52 (m, 1H), 1.36 (d, J = 6.5 Hz, 3H) 20 --
(Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.41 (d, J
= 7.9 Film) (m/z) Hz, 1H), 8.28 (d, J = 5.4 Hz, 1H), 7.31-7.23
3378, [M + H].sup.+ (m, 2H), 7.24-7.17 (m, 3H), 6.95 (d, J = 5.4
2935, calcd for Hz, 1H), 5.79-5.65 (m, 2H), 5.16 (dq, J = 2875,
C.sub.28H.sub.37N.sub.2O.sub.9, 9.6, 6.5 Hz, 1H), 4.64 (dt, J =
10.2, 7.6 Hz, 1749, 545.2494; 1H), 3.90 (s, 3H), 3.74-3.62 (m, 2H),
3.55- 1675, found, 3.48 (m, 1H), 3.48-3.35 (m, 2H), 3.31 (s, 1505
545.2490 3H), 2.62 (dd, J = 15.9, 3.4 Hz, 1H), 2.52 (dd, J = 15.9,
6.4 Hz, 1H), 2.44 (ddt, J = 13.5, 7.6, 3.6 Hz, 1H), 2.28 (tdd, J =
9.9, 6.5, 3.4 Hz, 1H), 2.06 (s, 3H), 2.01-1.80 (m, 2H), 1.77- 1.68
(m, 1H), 1.29 (d, J = 6.5 Hz, 3H) 21 -- -- HRMS-ESI .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 8.55 (d, J = 7.3 (m/z) Hz, 1H), 8.30
(d, J = 5.4 Hz, 1H), 7.20 (dd, J = [M + H].sup.+ 8.4, 5.6 Hz, 2H),
7.01-6.94 (m, 3H), 5.75 calcd for (d, J = 1.6 Hz, 2H), 5.17 (qd, J
= 6.6, 3.1 Hz, C.sub.25H.sub.30FN.sub.2O.sub.8, 1H), 4.70 (td, J =
7.7, 5.3 Hz, 1H), 3.96 (ddd, 505.1981; J = 11.1, 7.6, 2.8 Hz, 1H),
3.91 (s, 3H), 3.63 found, (dd, J = 10.7, 3.9 Hz, 1H), 3.50 (dd, J =
10.7, 505.1988 2.4 Hz, 1H), 3.45 (ddd, J = 10.8, 7.6, 2.5 Hz, 1H),
2.85 (dd, J = 13.6, 7.9 Hz, 1H), 2.77 (dd, J = 13.6, 8.4 Hz, 1H),
2.56-2.39 (m, 1H), 2.08 (s, 3H), 1.98-1.85 (m, 1H), 1.78-1.67 (m,
1H), 1.25 (d, J = 6.6 Hz, 3H) .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta. -117.25 22 -- -- HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.41 (d, J = 7.8 (m/z) Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H),
7.14 (dd, J = [M + H].sup.+ 8.5, 5.4 Hz, 2H), 7.03-6.92 (m, 3H),
5.80- calcd for 5.66 (m, 2H), 5.16 (dq, J = 9.4, 6.5 Hz, 1H),
C.sub.27H.sub.34FN.sub.2O.sub.8, 4.63 (dt, J = 10.0, 7.6 Hz, 1H),
3.91 (s, 3H), 533.2294; 3.64 (t, J = 10.2 Hz, 1H), 3.57-3.50 (m,
1H), found, 3.41 (td, J = 10.2, 3.0 Hz, 1H), 2.63-2.55 (m, 533.2297
1H), 2.51 (dd, J = 15.8, 6.5 Hz, 1H), 2.42 (ddd, J = 14.0, 7.4, 3.8
Hz, 1H), 2.24-2.12 (m, 1H), 2.07 (s, 3H), 1.78-1.53 (m, 3H), 1.28
(d, J = 6.5 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H) .sup.19F NMR (376
MHz, CDCl.sub.3) .delta. -116.89 23 -- -- HRMS-ESI .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.40 (d, J = 8.0 (m/z) Hz, 1H), 8.28 (d, J
= 5.3 Hz, 1H), 7.14 (dd, J = [M + H].sup.+ 8.5, 5.5 Hz, 2H), 6.99
(t, J = 8.7 Hz, 2H), calcd for 6.95 (d, J = 5.4 Hz, 1H), 5.85-5.61
(m, 2H), C.sub.29H.sub.38FN.sub.2O.sub.8, 5.16 (dq, J = 9.5, 6.5
Hz, 1H), 4.63 (dt, J = 561.2607; 10.2, 7.6 Hz, 1H), 3.91 (s, 3H),
3.71-3.57 found, (m, 1H), 3.56-3.38 (m, 2H), 2.59 (dd, J = 561.2602
15.6, 3.8 Hz, 1H), 2.50 (dd, J = 15.8, 6.6 Hz, 1H), 2.46-2.37 (m,
1H), 2.23-2.12 (m, 1H), 2.06 (s, 3H), 1.76-1.64 (m, 1H), 1.64-1.50
(m, 2H), 1.44 (tdd, J = 11.0, 8.8, 6.1 Hz, 1H), 1.28 (d, J = 6.4
Hz, 3H), 1.38-1.16 (m, 3H), 0.88 (t, J = 7.0 Hz, 3H) .sup.19F NMR
(376 MHz, CDCl.sub.3) .delta. -116.89 24 -- -- HRMS-ESI .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 8.42 (d, J = 7.9 (m/z) Hz, 1H), 8.29
(d, J = 5.4 Hz, 1H), 7.33-7.25 [M + H].sup.+ (m, 2H), 7.23-7.17 (m,
1H), 7.18-7.11 (m, calcd for 2H), 7.01 (dd, J = 8.5, 5.5 Hz, 2H),
6.97- C.sub.33H.sub.38FN.sub.2O.sub.8, 6.86 (m, 3H), 5.84-5.64 (m,
2H), 5.14 (dq, J = 609.2607; 9.4, 6.4 Hz, 1H), 4.65 (dt, J = 10.2,
7.7 Hz, found, 1H), 3.91 (s, 3H), 3.75-3.58 (m, 2H), 3.53 609.2599
(td, J = 10.6, 2.3 Hz, 1H), 2.79 (ddd, J = 13.7, 9.0, 4.6 Hz, 1H),
2.67-2.37 (m, 4H), 2.25- 2.12 (m, 1H), 2.07 (s, 3H), 2.02-1.68 (m,
3H), 1.29 (d, J = 6.5 Hz, 3H) .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta. -116.77 25 -- -- HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.41 (d, J = 7.9 (m/z) Hz, 1H), 8.30-8.25 (m, 1H), 7.15
(dd, J = [M + H].sup.+ 8.5, 5.4 Hz, 2H), 7.01-6.92 (m, 3H), 5.80-
calcd for 5.68 (m, 2H), 5.14 (dq, J = 9.2, 6.5 Hz, 1H),
C.sub.28H.sub.36FN.sub.2O.sub.9, 4.64 (dt, J = 9.3, 7.6 Hz, 1H),
3.91 (s, 3H), 563.2399; 3.74-3.62 (m, 2H), 3.57-3.35 (m, 3H), 3.31
found, (s, 3H), 2.59 (dd, J = 16.1, 3.3 Hz, 1H), 2.50 563.2400 (dd,
J = 15.9, 6.4 Hz, 1H), 2.43 (ddd, J = 14.1, 7.4, 4.0 Hz, 1H), 2.22
(dtd, J = 10.1, 6.5, 3.3 Hz, 1H), 2.06 (s, 3H), 1.97-1.85 (m, 2H),
1.71 (dtd, J = 14.4, 11.9, 11.3, 2.7 Hz, 1H), 1.29 (d, J = 6.5 Hz,
3H) .sup.19F NMR 376 MHz, CDCl.sub.3) .delta. -116.86 26 48-54 --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.41 (d, J = 8.0
(m/z) Hz, 1H) 8.29 (d, J = 5.3 Hz, 1H), 7.30-7.25 [M + H].sup.+ (m,
2H), 7.23-7.15 (m, 3H), 6.95 (d, J = 5.4 calcd for Hz, 1H), 5.75
(d, J = 1.0 Hz, 2H), 5.09 (dq, J = C.sub.31H.sub.43N.sub.2O.sub.8,
9.5, 6.4 Hz, 1H), 4.65 (app dt, J = 10.1, 7.7 571.3014; Hz, 1H),
3.91 (s, 3H), 3.69-3.51 (m, 3H), found, 2.82 (ddd, J = 13.7, 9.0,
4.7 Hz, 1H), 2.65- 571.3023 2.52 (m, 1H), 2.51-2.39 (m, 1H), 2.07
(s, 3H), 1.89-1.74 (m, 4H), 1.40-1.20 (m, 6H), 1.02-0.88 (m, 2H),
0.82 (d, J = 6.6 Hz, 3H), 0.79 (d, J = 6.6 Hz, 3H) 27 49-54 --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.41 (d, J = 8.0
(m/z) Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 7.19-7.10 [M + H].sup.+
(m, 2H), 7.01-6.92 (m, 3H), 5.75 (s, 2H), calcd for 5.08 (dq, J =
9.6, 6.5 Hz, 1H), 4.64 (app dt, J =
C.sub.31H.sub.42FN.sub.2O.sub.8, 10.3, 7.8 Hz, 1H), 3.91 (s, 3H),
3.68-3.49 589.2920; (m, 3H), 2.78 (ddd, J = 13.4, 8.6, 4.5 Hz, 1H),
found, 2.63-2.50 (m, 1H), 2.45 (ddd, J = 13.6, 7.6, 589.2935 3.5
Hz, 1H), 2.07 (s, 3H), 1.90-1.67 (m, 4H), 1.39-1.15 (m, 6H)
1.01-0.86 (m, 2H), 0.82 (d, J = 6.6 Hz, 3H), 0.79 (d, J = 6.6 Hz,
3H) 28 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
8.52 (d, J = 7.3 Film) (m/z) Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H),
7.45-7.15 3382, [M + H].sup.+ (m, 9H), 6.95 (d, J = 5.4 Hz, 1H),
5.78-5.69 2934, calcd for (m, 2H) 4.92 (qd, J = 6.6, 4.4 Hz, 1H),
4.63 2869, C.sub.31H.sub.35N.sub.2O.sub.8, (app td, J = 7.5, 5.3
Hz, 1H), 3.90 (s, 3H), 3.82 1747, 563.2388; (ddd, J = 10.9, 7.7,
2.7 Hz, 1H), 3.39-3.22 1675, found, (m, 3H), 2.90 (dd, J = 13.6,
6.0 Hz, 1H), 2.78 1501, 563.2397 (dd, J = 13.6, 9.4 Hz, 1H), 2.43
(dddd, J = 1200 14.4, 7.9, 5.4, 2.6 Hz, 1H), 2.06 (s, 3H), 1.83
(app dtd, J = 14.8, 7.5, 2.7 Hz, 1H), 1.44- 1.33 (m, 1H), 0.91 (d,
J = 6.6 Hz, 3H) 29 55-60 -- HRMS-ESI .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.35 (d, J = 8.0 (m/z) Hz, 1H), 8.26 (d, J =
5.4 Hz, 1H), 7.34-7.15 [M + H].sup.+ (m, 5H), 6.93 (d, J = 5.4 Hz,
1H), 5.72 (s, 2H), calcd for 5.15 (dq, J = 9.7, 6.4 Hz, 1H), 4.63
(app dt, J = C.sub.30H.sub.41N.sub.2O.sub.8, 9.5, 7.6 Hz, 1H), 4.04
(app td, J = 10.5, 3.0 557.2857; Hz, 1H) 3.89 (s, 3H), 3.60 (app t,
J = 10.0 Hz, found, 1H), 3.44-3.35 (m, 1H), 2.93 (dd, J = 15.5,
557.2867 3.0 Hz, 1H), 2.83 (dd, J = 15.5, 10.4 Hz, 1H), 2.36-2.24
(m, 1H), 2.05 (s, 3H), 2.00-1.88 (m, 1H), 1.67-1.53 (m, 1H),
1.49-1.34 (m, 6H), 1.30-1.13 (m, 2H), 0.89 (d, J = 6.7 Hz, 3H),
0.87 (d, J = 6.5 Hz, 3H) 30 86-88 -- HRMS-ESI .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.51 (d, J = 7.4 (m/z) Hz, 1H), 8.28 (d, J =
5.3 Hz, 1H), 6.95 (d, J = [M + H].sup.+ 5.4 Hz, 1H), 5.79-5.70 (m,
2H), 5.11 (qd, J = calcd for 6.6, 5.0 Hz, 1H), 4.67 (app td, J =
7.9, 5.7 Hz, C.sub.23H.sub.35N.sub.2O.sub.8, 1H), 3.91 (s, 3H),
3.85 (ddd, J = 10.2, 6.9, 2.7 467.2388; Hz, 1H), 3.63 (dd, J =
11.0, 5.4 Hz, 1H), 3.58 found (dd, J = 11.0, 3.5 Hz, 1H), 3.50
(ddd, J = 10.8, 467.2394 8.0, 2.3 Hz, 1H), 2.54-2.42 (m, 1H), 2.07
(s, 3H), 1.93-1.79 (m, 1H), 1.65-1.34 (m, 4H), 1.33 (d, J = 6.6 Hz,
3H), 1.22-1.11 (m, 2H), 0.88 (app dd, J = 6.6, 4.1 Hz, 6H) 31 -- --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.41 (d, J = 8.0
(m/z) Hz, 1H), 8.29 (d, J = 5.4 Hz, 1H), 7.32-7.25 [M + H].sup.+
(m, 2H), 7.23-7.16 (m, 3H), 6.95 (d, J = 5.4 calcd for Hz, 1H),
5.75 (d, J = 1.1 Hz, 2H), 5.09 (dq, J =
C.sub.30H.sub.40N.sub.2O.sub.8, 9.6, 6.5 Hz, 1H), 4.65 (dt, J =
10.3, 7.7 Hz, 557.2857; 1H), 3.91 (s, 3H), 3.68-3.53 (m, 3H), 2.83
found, (ddd, J = 13.9, 9.1, 4.8 Hz, 1H), 2.58 (dt, J = 557.2849
13.9, 8.3 Hz, 1H), 2.51-2.39 (m, 1H), 2.07 (s, 3H) 1.93-1.71 (m,
4H), 1.31 (d, J = 6.4 Hz, 3H, 1.28-1.14 (m, 4H), 1.13-1.03 (m, 2H),
0.84 (t, J = 7.2 Hz, 3H) .sup.13C NMR (101 MHz, CDCl.sub.3) .delta.
172.14, 170.26, 163.09, 160.18, 145.86, 143.76, 142.68, 141.84,
128.43, 128.40, 125.93, 109.54, 89.51, 79.41, 74.93, 57.66, 56.18,
50.12, 43.37, 34.12, 32.24, 31.45, 27.84, 32 -- (Thin HRMS-ESI
27.47 23.32, 20.90, 19.38, 13.81 Film) (m/z) .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.40 (d, J = 7.9 3379, [M + H].sup.+ Hz, 1H),
8.29 (d, J = 5.4 Hz, 1H), 6.95 (d, J = 2936, calcd for 5.4 Hz, 1H),
5.74 (d, J = 0.8 Hz, 2H), 5.14 2253,
C.sub.27H.sub.40N.sub.2O.sub.10, dq, J = 9.5, 6.5 Hz, 1H), 4.65
(dt, J = 9.7, 7.5 1735, 553.2756; Hz, 1H), 4.30 (dd, J = 12.5, 2.5
Hz, 1H), 4.20 1673 found, (dd, J = 12.5, 7.7 Hz, 1H), 3.91 (s, 3H),
3.90- 553.2763 3.86 (m, 1H), 3.76 (t, J = 10.0 Hz, 1H), 3.54 (ddd,
J = 9.4, 4.4, 2.3 Hz, 1H), 2.66-2.53 (m, 1H), 2.46-2.36 (m, 1H),
2.07 (s, 3H), 1.97 (t, J = 10.3 Hz, 1H), 1.80-1.69 (m, 1H), 1.36
(d, J = 6.5 Hz, 4H), 1.34-1.22 (m, 5H), 1.19 (dd, J = 7.0, 1.1 Hz,
6H), 0.90 (d, J = 6.9 Hz, 3H) 33 -- (Thin HRMS-ESI .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.52 (d, J = 7.5 Film) (m/z) Hz, 1H), 8.28
(d, J = 5.4 Hz, 1H), 6.94 (d, J = 3378, [M + H].sup.+ 5.4 Hz, 1H)
5.75 (d, J = 1.7 Hz, 2H), 5.11 (q, 2955, calcd for J = 6.3 Hz, 1H),
4.72-4.63 (m, 1H), 3.91 (s, 2929, C.sub.22H.sub.32N.sub.2O.sub.8,
3H), 3.88-3.81 (m, 1H), 3.60 (qd, J = 11.0, 2870, 453.2231; 4.5 Hz,
2H), 3.55-3.45 (m, 1H), 2.55-2.42 1745, found, (m, 1H), 2.07 (s,
3H), 1.93-1.80 (m, 1H), 1675 453.2234 1.62 (s, 1H), 1.51-1.39 (m,
1H), 1.32 (d, J = 6.7 Hz, 3H), 1.31-1.22 (m, 5H), 0.90 (t, J = 6.9
Hz, 3H) 34 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.40 (d, J = 7.9 Film) (m/z) Hz, 1H), 8.28 (d, J = 5.4 Hz,
1H), 6.95 (d, J = 3371, [M].sup.+ 5.4 Hz, 1H), 5.74 (s, 2H),
5.18-5.05 (m, 1H), 2957, calcd for 4.69-4.57 (m, 1H), 3.91 (s, 3H),
3.64-3.53 1754, C.sub.24H.sub.36N.sub.2O.sub.8, (m, 1H), 3.52-3.41
(m, 2H), 2.47-2.35 (m, 1677, 480.2472; 1H), 2.07 (s, 3H), 1.85-1.42
(m, 4H), 1.33 1506, found, (d, J = 6.5 Hz, 3H), 1.31-1.09 (m, 6H),
0.98 1374, 480.2475 (t, J = 7.2 Hz, 3H), 0.90 (t, J = 6.9 Hz, 3H)
1202 .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 172.12, 170.20,
163.05, 160.15, 145.85, 143.69, 142.66, 109.54, 89.45, 82.04,
74.96, 57.41, 56.17, 50.12, 43.61, 34.11, 27.96, 27.76, 23.36,
22.67, 20.85, 19.37, 13.84, 10.83 35 -- (Thin HRMS-ESI .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 8.39 (d, J = 7.9 Film) (m/z) Hz, 1H),
8.29 (d, J = 5.4 Hz, 1H), 7.36-7.25 3370, [M].sup.+ (m, 2H),
7.03-6.87 (m, 4H), 5.74 (s, 2H), 1752, calcd for 5.25-5.11 (m, 1H),
4.73-4.60 (m, 1H), 4.21- 1674, C.sub.29H.sub.38N.sub.2O.sub.9, 4.06
(m, 2H), 4.05-3.97 (m, 1H), 3.91- 1499, 558.2577; 3.83 (m, 1H),
3.90 (s, 3H), 3.64-3.56 (m,
1370, found, 1H), 2.44-2.31 (m, 1H), 2.30-2.18 (m, 1H), 1242
558.2569 2.07 (s, 3H), 1.81-1.67 (m, 1H), 1.39 (d, J = 6.4 Hz, 3H),
1.36-1.12 (m, 6H), 0.88 (t, J = 6.8 Hz, 3H) .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 172.10 170.24, 163.06, 160.18, 158.37, 145.85,
143.75, 142.63, 129.54, 121.15, 114.54, 109.58, 89.47, 78.30,
74.61, 67.37, 60.44, 56.19, 50.30, 39.97, 34.25, 27.55, 27.25,
23.34, 20.88, 19.30, 13.85 36 -- (Thin HRMS-ESI .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 8.63 (d, J = 7.4 Film) (m/z) Hz, 1H), 8.29
(d, J = 5.3 Hz, 1H), 7.32-7.26 3378, [M + H].sup.+ (m, 2H),
7.26-7.22 (m, 2H), 7.19 (tt, J = 6.1, 2975, calcd for 1.5 Hz, 1H),
6.95 (d, J = 5.4 Hz, 1H), 5.89- 2932,
C.sub.27H.sub.35N.sub.2O.sub.8, 5.62 (m, 2H), 5.19 (qd, J = 6.6,
3.7 Hz, 1H), 2872, 515.2388; 4.70 (td, J = 7.7, 5.4 Hz, 1H), 3.94
(ddd, J = 1742, found, 11.4, 7.4, 2.8 Hz, 1H), 3.89 (s, 3H), 3.63
(dd, J = 1675, 515.2398 10.7, 4.2 Hz, 1H), 3.50 (dd, J = 10.8, 2.6
Hz, 1501 1H), 3.45 (ddd, J = 11.2, 7.7, 2.5 Hz, 1H), 2.88 (dd, J =
13.5, 7.7 Hz, 1H), 2.77 (dd, J = 13.5, 8.5 Hz, 1H), 2.55 (hept, J =
7.0 Hz, 1H), 2.48 (dddd, J = 12.8, 7.7, 5.1, 2.5 Hz, 1H), 1.94-1.86
(m, 1H), 1.86-1.78 (m, 1H), 1.25 (d, J = 6.6 Hz, 3H), 1.14 (d, J =
7.0 Hz, 6H) 37 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.42 (d, J = 7.9 Film) (m/z) Hz, 1H), 8.25 (d, J = 5.3 Hz,
1H), 7.36-7.22 3379, [M + H].sup.+ (m, 3H), 7.27-7.21 (m, 4H),
7.21-7.15 (m, 2975, calcd for 3H), 6.91 (d, J = 5.4 Hz, 1H),
5.83-5.64 (m, 2936, C.sub.34H.sub.41N.sub.2O.sub.8, 2H), 5.22 (dq,
J = 9.6, 6.5 Hz, 1H), 4.64 (dt, J = 1744, 605.2857; 9.7, 7.5 Hz,
1H), 4.00 (td, J = 10.6, 2.5 Hz, 1675, found, 1H), 3.86 (s, 3H),
3.66 (t, J = 10.0 Hz, 1H), 1498 605.2868 3.43 (ddd, J = 9.6, 4.6,
2.3 Hz, 1H), 3.06- 2.97 (m, 1H), 2.87 (dd, J = 15.7, 10.9 Hz, 1H),
2.76 (dd, J = 15.8, 3.8 Hz, 1H), 2.66 (dd, J = 15.8, 6.2 Hz, 1H),
2.52 (p, J = 7.0 Hz, 1H), 2.39 (tdd, J = 9.9, 6.3, 3.8 Hz, 1H),
2.34- 2.25 (m, 1H), 1.65-1.53 (m, 1H), 1.37 (d, J = 6.5 Hz, 3H),
1.12 (d, J = 7.0 Hz, 6H) 38 -- -- HRMS-ESI .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.48 (d, J = 7.9 (m/z) Hz, 1H), 8.28 (d, J =
5.3 Hz, 1H), 7.31-7.24 [M + H].sup.+ (m, 2H), 7.20 (t, J = 7.3 Hz,
1H), 7.14 (d, J = calcd for 6.7 Hz, 2H), 7.01 (dd, J = 8.5, 5.5 Hz,
2H), C.sub.35H.sub.42FN.sub.2O.sub.8 6.97-6.89 (m, 3H), 5.82-5.72
(m, 2H), 5.14 637.2920; (dq, J = 9.5, 6.5 Hz, 1H), 4.65 (dt, J =
10.2, found, 7.6 Hz, 1H), 3.89 (s, 3H), 3.73-3.65 (m, 1H), 637.2922
3.65-3.57 (m, 1H), 3.53 (td, J = 10.7, 2.3 Hz, 1H), 2.79 (ddd, J =
13.6, 8.9, 4.6 Hz, 1H), 2.52 (dtdd, J = 32.0, 15.7, 7.0, 4.4 Hz,
5H), 2.25-2.09 (m, 1H), 2.03-1.69 (m, 3H), 1.29 (d, J = 6.5 Hz,
3H), 1.14 (d, J = 7.0 Hz, 6H) .sup.19F NMR (376 MHz, CDCl.sub.3)
.delta. -116.81 39 49-54 -- HRMS-ESI .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.48 (d, J = 8.0 (m/z) Hz, 1H), 8.28 (d, J =
5.3 Hz, 1H), 7.19-7.10 [M + H].sup.+ (m, 2H), 7.01-6.91 (m, 3H),
5.83-5.74 (m, calcd for 2H), 5.08 (dq, J = 9.8, 6.4 Hz, 1H), 4.64
(app C.sub.33H.sub.46FN.sub.2O.sub.8, dt, J = 10.3, 7.8 Hz, 1H),
3.89 (s, 3H), 3.68- 617.3233; 3.49 (m, 3H), 2.78 (ddd, J = 13.5,
8.6, 4.6 Hz, found, 1H), 2.63-2.49 (m, 2H), 2.45 (ddd, J = 13.7,
617.3234 7.6, 3.5 Hz, 1H), 1.90-1.67 (m, 4H), 1.39- 1.11 (m, 12H),
1.01-0.85 (m, 2H), 0.82 (d, J = 6.6 Hz, 3H), 0.79 (d, J = 6.6 Hz,
3H) 40 54-59 -- HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
8.58 (d, J = 7.3 (m/z) Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H), 7.45-7.23
[M + H].sup.+ (m, 8H), 7.23-7.16 (m, 1H), 6.94 (d, J = 5.4 calcd
for Hz, 1H), 5.81-5.72 (m, 2H), 4.92 (qd, J =
C.sub.33H.sub.39N.sub.2O.sub.8, 6.6, 4.3 Hz, 1H), 4.62 (app td, J =
7.5, 5.3 Hz, 591.2701; 1H), 3.88 (s, 3H), 3.82 (ddd, J = 10.8, 7.7,
2.7 found, Hz, 1H), 3.39-3.22 (m, 3H), 2.90 (dd, J = 591.2713 13.6,
6.0 Hz, 1H), 2.78 (dd, J = 13.6, 9.4 Hz, 1H), 2.54 (hept, J = 7.0
Hz, 1H), 2.47-2.36 (m, 1H), 1.90-1.77 (m, 1H), 1.44-1.32 (m, 1H),
1.13 (d, J = 7.0 Hz, 6H), 0.91 (d, J = 6.6 Hz, 3H) 41 110-112 (Thin
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.46 (d, J = 8.0
Film) (m/z) Hz, 1H), 8.28 (d, J = 5.4 Hz, 1H), 7.35-7.24 3379,
[M].sup.+ (m, 2H), 7.02-6.89 (m, 4H), 5.82-5.73 (m, 2935, calcd for
2H), 5.25-5.12 (m, 1H), 4.71-4.60 (m, 1H), 1745,
C.sub.31H.sub.42N.sub.2O.sub.9, 4.21-4.06 (m, 2H), 4.06-3.97 (m,
1H), 3.93- 1676, 586.2890; 3.84 (m, 1H), 3.89 (s, 3H), 3.63-3.56
(m, 1498, found, 1H), 2.54 (hept, J = 7.0 Hz, 1H), 2.43-2.32 1317,
586.2882 (m, 1H), 2.29-2.19 (m, 1H), 1.81-1.67 (m, 1217 1H), 1.39
(d, J = 6.5 Hz, 3H), 1.37-1.17 (m, 6H), 1.14 (d, J = 7.0 Hz, 6H),
0.88 (t, J = 6.8 Hz, 3H) .sup.13C NMR (101 MHz, CDCl.sub.3) .delta.
176.21, 172.09, 163.02, 160.17, 158.37, 145.70, 143.99, 142.28,
129.54, 121.15, 114.54, 109.51, 89.83, 78.31, 74.60, 67.39, 60.49,
56.13, 50.29, 39.99, 34.28, 33.85, 27.56, 27.26, 23.35, 19.30,
18.69, 13.85 42 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.58 (d, J = 7.4 Film) (m/z) Hz, 1H), 8.29 (d, J = 5.3 Hz,
1H), 7.32-7.28 3378, [M + H].sup.+ (m, 1H), 7.27-7.22 (m, 3H),
7.22-7.17 (m, 2976, calcd for 1H), 6.96 (d, J = 5.4 Hz), 5.93-5.71
(m, 2928, C.sub.27H.sub.35N.sub.2O.sub.9, 2H), 5.19 (qd, J = 6.6,
3.7 Hz, 1H), 4.68 (td, J = 2870, 531.2337; 7.7, 5.3 Hz, 1H), 4.10
(s, 2H), 4.00-3.89 1772, found, (m, 1H), 3.90 (s, 3H), 3.63 (dd, J
= 11.1, 4.6 1740, 531.2349 Hz, 1H), 3.59 (q, J = 6.9 Hz, 2H), 3.50
(dd, J = 1675, 10.8, 2.6 Hz, 1H), 3.45 (ddd, J = 11.3, 7.7, 1501
2.6 Hz, 1H), 2.87 (dd, J = 13.5, 7.7 Hz, 1H), 2.77 (dd, J = 13.5,
8.5 Hz, 1H), 2.48 (dddd, J = 14.3, 7.7, 5.4, 2.5 Hz, 1H), 1.96-1.86
(m, 1H), 1.86-1.77 (m, 1H), 1.25 (d, J = 6.8 Hz, 3H), 1.22 (t, J =
7.0 Hz, 3H) 43 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.41 (d, J = 8.0 Film) (m/z) Hz, 1H) 8.28 (d, J = 5.4 Hz,
1H), 7.32-7.27 3378, [M + H].sup.+ (m, 2H), 7.23-7.15 (m, 3H), 6.94
(d, J = 5.5 2933, calcd for Hz, 1H), 5.88-5.78 (m, 2H), 5.18 (dq, J
= 2873, C.sub.30H.sub.41N.sub.2O.sub.9, 9.4, 6.5 Hz, 1H), 4.61 (dt,
J = 10.2, 7.7 Hz, 1744, 573.2807; 1H), 4.09 (s, 2H), 3.90 (s, 3H),
3.68-3.61 (m, 1675, found, 1H), 3.58 (q, J = 7.0 Hz, 2H), 3.54-3.44
(m, 1502 573.2809. 2H), 2.63 (dd, J = 15.7, 3.4 Hz, 1H), 2.51 (dd,
J = 15.8, 6.7 Hz, 1H), 2.41 (ddd, J = 14.0, 7.6, 3.7 Hz, 1H), 2.22
(tdd, J = 9.9, 6.7, 3.3 Hz, 1H), 1.77-1.43 (m, 5H), 1.28 (d, J =
6.5 Hz, 3H), 1.22 (t, J = 7.0 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H) 44
-- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.37
(d, J = 8.0 Film) (m/z) Hz, 1H), 8.25 (d, J = 5.4 Hz, 1H),
7.36-7.25 3379, [M + H].sup.+ (m, 3H), 7.26-7.21 (m, 4H), 7.20-7.16
(m, 2977, calcd for 3H), 6.92 (d, J = 5.4 Hz, 1H), 5.80 (s, 2H),
2935, C.sub.34H.sub.41N.sub.2O.sub.9, 5.22 (dq, J = 9.5, 6.5 Hz,
1H), 4.62 (dt, J = 2880, 621.2807; 9.6, 7.5 Hz, 1H), 4.08 (s, 2H),
4.00 (td, J = 1772, found, 10.6, 2.5 Hz, 1H), 3.88 (s, 3H), 3.66
(t, J = 1744, 621.2819 10.0 Hz, 1H), 3.57 (q, J = 7.0 Hz, 2H), 3.43
1675, (ddd, J = 9.3, 4.5, 2.2 Hz, 1H), 3.08-2.96 (m, 1498 1H), 2.87
(dd, J = 15.7, 10.9 Hz, 1H), 2.76 (dd, J = 15.8, 3.8 Hz, 1H), 2.67
(dd, J = 15.8, 6.2 Hz, 1H), 2.39 (tdd, J = 9.9, 6.2, 3.8 Hz, 1H),
2.34-2.25 (m, 1H), 1.59 (dddd, J = 14.1, 10.8, 9.7, 2.2 Hz, 1H),
1.37 (d, J = 6.5 Hz, 3H), 1.21 (t, J = 7.0 Hz, 3H) 45 -- --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.43 (d, J = 8.0
(m/z) Hz, 1H), 8.29 (d, J = 5.4 Hz, 1H), 7.36-7.25 [M + H].sup.+
(m, 2H), 7.23-7.16 (m, 3H), 6.95 (d, J = 5.4 calcd for Hz, 1H),
5.83 (s, 2H), 5.09 (dq, J = 9.6, 6.5
C.sub.32H.sub.44N.sub.2O.sub.9, Hz, 1H), 4.63 (dt, J = 10.2, 7.8
Hz, 1H), 4.10 601.312; (s, 2H), 3.91 (s, 3H), 3.70-3.50 (m, 5H),
2.83 found, (ddd, J = 13.9, 9.0, 4.8 Hz, 1H), 2.58 (dt, J =
601.3108 13.8, 8.3 Hz, 1H), 2.44 (ddd, J = 14.0, 7.6, 3.6 Hz, 1H),
1.94-1.69 (m, 4H), 1.31 (d, J = 6.5 Hz, 3H), 1.28-1.12 (m, 7H),
1.09 (ddt, J = 14.9, 7.3, 4.6 Hz, 2H), 0.84 (t, J = 7.2 Hz, 3H)
.sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 172.11, 170.04, 163.02,
160.10, 145.90, 143.74, 142.50, 141.84, 128.43, 128.40, 125.93,
109.65, 89.53, 79.42, 74.94, 67.80, 67.19, 57.66, 56.22, 50.09,
43.37, 34.12, 32.24, 31.46, 27.85, 27.48, 23.32, 19.39, 15.02,
13.81 46 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.42 (d, J = 8.0 Film) (m/z) Hz, 1H), 8.28 (d, J = 5.4 Hz,
1H), 6.95 (d, J = 3377, [M].sup.+ 5.4 Hz, 1H), 5.82 (s, 2H),
5.17-5.05 (m, 1H), 2933, calcd for 4.66-4.55 (m, 1H), 4.10 (s, 2H),
3.90 (s, 3H), 1745, C.sub.26H.sub.40N.sub.2O.sub.9, 3.64-3.53 (m,
3H), 3.51-3.42 (m, 2H), 2.46- 1676, 524.2734; 2.34 (m, 1H),
1.84-1.41 (m, 4H), 1.33 (d, J = 1505, found, 6.5 Hz, 3H), 1.30-1.10
(m, 6H), 1.23 (t, J = 1376, 527.2741 7.0 Hz, 3H), 0.98 (t, J = 7.3
Hz, 3H), 0.89 (t, J = 1210 6.9 Hz, 3H) .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 172.10, 170.00, 162.99, 160.07, 145.89, 143.68,
142.50, 109.64, 89.49, 82.05, 74.98, 67.77, 67.15, 57.41, 56.20,
50.10, 43.62, 34.12, 27.97, 27.77, 23.36, 22.69, 19.38, 15.00,
13.85, 10.83 47 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 8.41 (d, J = 8.0 Film) (m/z) Hz, 1H), 8.28 (d, J = 5.4 Hz,
1H), 7.33-7.28 3371, [M + H].sup.+ (m, 2H), 7.00-6.91 (m, 4H), 5.82
(s, 2H), 1745, calcd for 5.25-5.13 (m, 1H), 4.70-4.59 (m, 1H),
4.21- 1675, C.sub.31H.sub.43N.sub.2O.sub.10, 4.06 (m, 2H), 4.09 (s,
2H), 4.05-3.98 (m, 1498, 603.2918; 1H), 3.91-3.83 (m, 1H), 3.90 (s,
3H), 3.64- 1377, found, 3.56 (m, 1H), 3.59 (q, J = 7.0 Hz, 2H),
2.41- 1219 603.2905 2.31 (m, 1H), 2.29-2.19 (m, 1H), 1.81-1.67 (m,
1H), 1.39 (d, J = 6.5 Hz, 3H), 1.37-1.15 (m, 6H), 1.22 (t, J = 7.0
Hz, 3H), 0.88 (t, J = 6.8 Hz, 3H) .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 172.07, 170.03, 162.99, 160.10, 158.36, 145.88,
143.74, 142.44, 129.53, 121.15, 114.53, 109.68, 89.49, 78.31,
74.62, 67.78, 67.38, 67.16, 60.46, 56.22, 50.27, 39.98, 34.24,
27.55, 27.25, 23.34, 19.30, 15.01, 13.85 48 -- (Thin HRMS-ESI
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 8.75 (d, J = 7.6 Film)
(m/z) Hz, 1H), 8.36 (d, J = 5.4 Hz, 1H), 7.32-7.27 3380, [M +
H].sup.+ (m, 2H) 7.26-7.22 (m, 2H), 7.22-7.17 (m, 2975, calcd for
1H), 7.01 (d, J = 5.5 Hz, 1H), 5.18 (qd, J = 2929,
C.sub.26H.sub.33N.sub.2O.sub.8, 6.6, 3.6 Hz, 1H), 4.65 (td, J =
7.8, 5.4 Hz, 1H), 2871, 501.2231; 4.48 (d, J = 0.6 Hz, 2H),
3.95-3.91 (m, 1H), 1785, found, 3.89 (s, 3H), 3.73 (q, J = 7.0 Hz,
2H), 3.63 1739, 501.2239 (dd, J = 10.7, 4.2 Hz, 1H), 3.49 (dd, J =
10.8, 1676, 2.6 Hz, 1H), 3.43 (ddd, J = 11.3, 7.6, 2.5 Hz, 1507
1H), 2.87 (dd, J = 13.5, 7.7 Hz, 1H), 2.77 (dd, J = 13.5, 8.4 Hz,
1H), 2.45 (dddd, J = 14.4, 7.7, 5.4, 2.5 Hz, 1H), 1.92-1.84 (m,
1H), 1.84-1.76 (m, 1H), 1.28 (t, J = 7.0 Hz, 3H), 1.24 (d, J = 6.6
Hz, 3H) 49 -- (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 12.13 (s, 1H), Film) (m/z) 8.74 (d, J = 7.5 Hz, 1H), 8.00
(d, J = 5.2 Hz, 3367, [M + H].sup.+ 1H), 7.33-7.22 (m, 4H),
7.22-7.17 (m, 1H), 3026, calcd for 6.87 (d, J = 5.2 Hz, 1H), 5.20
(qd, J = 6.6, 3.6 2971, C.sub.22H.sub.27N.sub.2O.sub.6, Hz, 1H),
4.68 (td, J = 7.8, 5.4 Hz, 1H), 3.99- 2929, 415.1864; 3.94 (m, 1H),
3.93 (s, 3H), 3.65 (dd, J = 10.8, 2870, found, 4.3 Hz, 1H), 3.50
(dd, J = 10.8, 2.6 Hz, 1H), 1738, 415.1867 3.48-3.44 (m, 1H), 2.88
(dd, J = 13.5, 7.7 1648, Hz, 1H), 2.77 (dd, J = 13.5, 8.4 Hz, 1H),
2.49 1526 (dddd, J = 14.4, 7.7, 5.4, 2.5 Hz, 1H), 1.93 (dtd, J =
14.3, 7.9, 2.7 Hz, 1H), 1.83 (ttd, J = 8.0, 4.0, 2.5 Hz, 1H), 1.26
(d, J = 6.6 Hz, 3H) 50 52-56 -- HRMS-ESI .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 12.12 (s, 1H), (m/z) 8.58 (d, J = 8.1 Hz, 1H),
7.99 (d, J = 5.1 Hz, [M + H].sup.+ 1H), 7.33-7.27 (m, 2H),
7.23-7.14 (m, 3H), calcd for 6.86 (d, J = 5.2 Hz, 1H), 5.20 (dq, J
= 9.5, 6.5 C.sub.25H.sub.33N.sub.2O.sub.6, Hz, 1H), 4.60 (dt, J =
10.3, 7.7 Hz, 1H), 3.93 457.2333; (s, 3H), 3.66 (dd, J = 11.1, 9.4
Hz, 1H), 3.60- found, 3.41 (m, 2H), 2.63 (dd, J = 15.7, 3.4 Hz,
1H), 457.2335 2.52 (dd, J = 15.8, 6.7 Hz, 1H), 2.39 (ddd, J = 14.0,
7.5, 3.7 Hz, 1H), 2.23 (tdd, J = 9.8, 6.7, 3.3 Hz, 1H), 1.82-1.44
(m, 3H), 1.30 (d, J = 6.6 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H) 51 --
(Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.13 (s,
1H), Film) (m/z) 8.59 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 5.1 Hz,
3367, [M + H].sup.+ 1H), 7.29 (t, J = 7.3 Hz, 2H), 7.24-7.14 (m,
2935, calcd for 3H), 6.86 (d, J = 5.2 Hz, 1H), 5.19 (dq, J = 2872,
C.sub.26H.sub.35N.sub.2O.sub.6, 9.5, 6.5 Hz, 1H), 4.60 (dt, J =
10.3, 7.7 Hz, 1743, 471.2490; 1H), 3.93 (s, 3H), 3.69-3.61 (m, 1H),
3.58- 1649, found, 3.41 (m, 2H), 2.62 (dd, J = 15.8, 3.2 Hz, 1H),
1527, 471.2499 2.52 (dd, J = 15.8, 6.6 Hz, 1H), 2.44-2.34 1436 (m,
1H), 2.23 (tdd, J = 9.9, 6.6, 3.5 Hz, 1H), 1.82-1.66 (m, 1H),
1.66-1.52 (m, 2H), 1.51- 1.38 (m, 1H), 1.36-1.32 (m, 1H), 1.30 (d,
J = 6.5 Hz, 3H), 1.28-1.17 (m, 2H), 0.88 (t, J = 7.0 Hz, 3H) 52 --
(Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.11 (s,
1H), Film) (m/z) 8.53 (d, J = 8.1 Hz, 1H), 7.96 (d, J = 5.2 Hz,
3366, [M + H].sup.+ 1H), 7.34-7.27 (m, 2H), 7.24 (td, J = 7.4, 1.5
2936, calcd for Hz, 4H), 7.23-7.13 (m, 4H), 6.83 (d, J = 5.2 1743,
C.sub.29H.sub.33N.sub.2O.sub.6, Hz, 1H), 5.22 (dq, J = 9.5, 6.5 Hz,
1H), 4.60 1648, 505.2333; (dt, J = 9.4, 7.4 Hz, 1H), 4.01 (td, J =
10.6, 2.5 1575, found, Hz, 1H), 3.91 (s, 3H), 3.65 (t, J = 9.9 Hz,
1H), 1496, 505.2341 3.43 (ddd, J = 9.5, 4.7, 2.2 Hz, 1H), 3.02 (dd,
1436 J = 15.8, 2.5 Hz, 1H), 2.85 (dd, J = 15.7, 10.9 Hz, 1H), 2.76
(dd, J = 15.9, 3.9 Hz, 1H), 2.67 (dd, J = 15.8, 6.1 Hz, 1H), 2.40
(tdd, J = 9.9, 6.2, 3.9 Hz, 1H), 2.32-2.22 (m, 1H), 1.71- 1.52 (m,
1H), 1.38 (d, J = 6.4 Hz, 3H) 53 -- (Thin HRMS-ESI .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 12.11 (s, 1H), Film) (m/z) 8.59 (d, J =
8.0 Hz, 1H), 7.99 (d, J = 5.2 Hz, 3362, [M + H].sup.+ 1H), 7.29 (t,
J = 7.3 Hz, 2H), 7.20 (t, J = 8.0 2935, calcd for Hz, 3H), 6.86 (d,
J = 5.2 Hz, 1H), 5.17 (dq, J = 2876,
C.sub.25H.sub.33N.sub.2O.sub.7, 9.6, 6.5 Hz, 1H), 4.61 (dt, J =
10.1, 7.7 Hz, 1742, 473.2282; 1H), 3.94 (s, 3H), 3.75-3.63 (m, 2H),
3.60- 1649, found, 3.51 (m, 1H), 3.50-3.35 (m, 2H), 3.31 (s, 1528,
473.2278 3H), 2.63 (dd, J = 15.9, 3.5 Hz, 1H), 2.53 (dd, 1436 J =
15.9, 6.4 Hz, 1H), 2.46-2.35 (m, 1H), 2.29 (tdd, J = 9.9, 6.4, 3.5
Hz, 1H), 1.98 (dtd, J = 15.4, 7.9, 2.2 Hz, 1H), 1.92-1.82 (m, 1H),
1.82-1.70 (m, 1H), 1.31 (d, J = 6.5 Hz, 3H) 54 -- -- HRMS-ESI
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.12 (s, 1H), (m/z) 8.73
(d, J = 7.6 Hz, 1H), 8.01 (d, J = 5.2 Hz, [M + H].sup.+ 1H), 7.21
(dd, J = 8.4, 5.6 Hz, 2H), 6.97 (t, J = calcd for 8.7 Hz, 2H), 6.88
(d, J = 5.2 Hz, 1H), 5.18 C.sub.22H.sub.26FN.sub.2O.sub.6, (qd, J =
6.6, 3.1 Hz, 1H), 4.68 (td, J = 7.8, 5.3 433.1769; Hz, 1H),
4.02-3.95 (m, 1H), 3.94 (s, 3H), found, 3.65 (dd, J = 10.7, 4.0 Hz,
1H), 3.53-3.41 433.1773 (m, 2H), 2.86 (dd, J = 13.6, 7.9 Hz, 1H),
2.77 (dd, J = 13.7, 8.4 Hz, 1H), 2.49 (dddd, J = 15.0, 7.7, 5.4,
2.5 Hz, 1H), 1.94 (dtd, J = 14.3, 7.8, 2.7 Hz, 1H), 1.74 (ttd, J =
7.7, 3.7, 2.4 Hz, 1H), 1.26 (d, J = 6.6 Hz, 3H) .sup.19F NMR (376
MHz, CDCl.sub.3) .delta. -117.15 55 -- -- HRMS-ESI .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 12.13 (s, 1H), (m/z) 8.59 (d, J = 8.0 Hz,
1H), 7.99 (d, J = 5.2 Hz, [M + H].sup.+ 1H), 7.13 (dd, J = 8.5, 5.4
Hz, 2H), 6.98 (t, J = calcd for 8.6 Hz, 2H), 6.87 (d, J = 5.3 Hz,
1H), 5.18 C.sub.24H.sub.30FN.sub.2O.sub.6, (dq, J = 9.4, 6.5 Hz,
1H), 4.61 (dt, J = 10.1, 461.2082; 7.7 Hz, 1H), 3.93 (s, 3H), 3.65
(dd, J = 11.2, found, 9.3 Hz, 1H), 3.59-3.50 (m, 1H), 3.42 (td, J =
461.2074 10.2, 2.8 Hz, 1H), 2.60 (dd, J = 15.7, 3.7 Hz, 1H), 2.51
(dd, J = 15.8, 6.5 Hz, 1H), 2.40 (ddd, J = 13.7, 7.5, 3.9 Hz, 1H),
2.18 (tdd, J = 9.9, 6.6, 3.6 Hz, 1H), 1.83-1.70 (m, 1H), 1.70-1.55
(m, 2H), 1.29 (d, J = 6.5 Hz, 3H), 0.96 (t, J = 7.3 Hz, 3H)
.sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -116.79 56 -- --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.11 (s, 1H),
(m/z) 8.58 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 5.2 Hz, [M + H].sup.+
1H), 7.14 (dd, J = 8.5, 5.5 Hz, 2H), 6.99 (t, J = calcd for 8.6 Hz,
2H), 6.86 (d, J = 5.2 Hz, 1H), 5.18
C.sub.26H.sub.34FN.sub.2O.sub.6, (dq, J = 9.4, 6.5 Hz, 1H), 4.60
(dt, J = 10.3, 489.2395; 7.7 Hz, 1H), 3.94 (s, 3H), 3.70-3.58 (m,
1H), found, 3.57-3.44 (m, 2H), 2.65-2.55 (m, 1H), 2.51 489.2376
(dd, J = 15.8, 6.6 Hz, 1H), 2.39 (ddt, J = 13.4, 7.6, 3.7 Hz, 1H),
2.18 (dddd, J = 12.7, 9.9, 6.5, 3.5 Hz, 1H), 1.80-1.69 (m, 1H),
1.69-1.49 (m, 2H), 1.49-1.40 (m, 1H), 1.29 (d, J = 6.5 Hz, 3H),
1.36-1.21 (m, 3H), 0.88 (t, J = 7.0 Hz, 3H) .sup.19F NMR (376 MHz,
CDCl.sub.3) .delta. -116.81 57 -- -- HRMS-ESI .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 12.11 (s, 1H), (m/z) 8.59 (d, J = 8.0 Hz, 1H),
8.00 (d, J = 5.2 Hz, [M + H].sup.+ 1H), 7.29-7.25 (m, 2H),
7.22-7.17 (m, 1H), calcd for 7.17-7.12 (m, 2H), 7.01 (dd, J = 8.5,
5.5 Hz, C.sub.30H.sub.34FN.sub.2O.sub.6, 2H), 6.92 (t, J = 8.6 Hz,
2H), 6.87 (d, J = 5.2 537.2395; Hz, 1H), 5.15 (dq, J = 9.5, 6.5 Hz,
1H), 4.62 found, (dt, J = 10.4, 7.7 Hz, 1H), 3.94 (s, 3H), 3.76-
537.2375 3.67 (m, 1H), 3.67-3.60 (m, 1H), 3.54 (td, J = 10.6, 2.4
Hz, 1H), 2.79 (ddd, J = 13.7, 8.9, 4.7 Hz, 1H), 2.63-2.38 (m, 4H),
2.24-2.13 (m, 1H), 2.00-1.75 (m, 3H), 1.30 (d, J = 6.5 Hz, 3H)
.sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -116.71 58 -- --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.10 (d, J =
(m/z) 0.6 Hz, 1H), 8.58 (d, J = 8.0 Hz, 1H), 8.00 (d, [M + H].sup.+
J = 5.2 Hz, 1H), 7.15 (dd, J = 8.6, 5.4 Hz, 2H), calcd for 6.99 (t,
J = 8.6 Hz, 2H), 6.87 (d, J = 5.2 Hz,
C.sub.25H.sub.32FN.sub.2O.sub.7, 1H), 5.15 (dq, J = 9.5, 6.5 Hz,
1H), 4.61 (dt, J = 491.2188; 10.0, 7.6 Hz, 1H), 3.94 (s, 3H),
3.76-3.63 found, (m, 2H), 3.54 (ddd, J = 9.4, 4.3, 2.4 Hz, 1H),
491.2197 3.52-3.34 (m, 2H), 3.32 (s, 3H), 2.64-2.55 (m, 1H), 2.51
(dd, J = 15.9, 6.3 Hz, 1H), 2.46- 2.36 (m, 1H), 2.22 (tdd, J = 9.9,
6.4, 3.6 Hz, 1H), 1.91 (dddt, J = 21.1, 10.6, 8.6, 5.1 Hz, 2H),
1.76 (dddd, J = 13.7, 11.0, 9.8, 2.4 Hz, 1H), 1.30 (d, J = 6.5 Hz,
3H) .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -116.78 59 91-93 --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.15 (d, J =
(m/z) 0.6 Hz, 1H), 8.60 (d, J = 8.1 Hz, 1H), 8.00 (d, [M + H].sup.+
J = 5.2 Hz, 1H), 7.33-7.23 (m, 2H), 7.23- calcd for 7.15 (m, 3H),
6.87 (d, J = 5.2 Hz, 1H), 5.11 C.sub.28H.sub.39N.sub.2O.sub.6, (dq,
J = 9.6, 6.4 Hz, 1H), 4.67-4.56 (m, 1H), 499.2803; 3.94 (s, 3H),
3.70-3.53 (m, 3H), 2.82 (ddd, J = found, 13.6, 8.7, 4.6 Hz, 1H),
2.65-2.53 (m, 1H), 499.2811 2.48-2.37 (m, 1H), 1.90-1.73 (m, 4H),
1.41- 1.16 (m, 6H), 1.02-0.89 (m, 2H), 0.82 (d, J = 6.5 Hz, 3H),
0.80 (d, J = 6.6 Hz, 3H) 60 86-88 -- HRMS-ESI .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 12.14 (s, 1H), (m/z) 8.60 (d, J = 8.1 Hz, 1H),
8.00 (d, J = 5.2 Hz, [M + H].sup.+ 1H), 7.17-7.11 (m, 2H),
7.01-6.93 (m, 2H), calcd for 6.87 (dd, J = 5.3, 0.7 Hz, 1H), 5.10
(dq, J = C.sub.28H.sub.38FN.sub.2O.sub.6, 9.6, 6.5 Hz, 1H), 4.61
(app dt, J = 10.2, 7.8 517.2708; Hz, 1H), 3.94 (s, 3H), 3.70-3.50
(m, 3H), found, 2.78 (ddd, J = 13.4, 8.5, 4.5 Hz, 1H), 2.63-
517.2693 2.51 (m, 1H), 2.48-2.37 (m, 1H), 1.91-1.67 (m, 4H),
1.41-1.15 (m, 6H), 1.02-0.88 (m, 2H), 0.82 (d, J = 6.6 Hz, 3H),
0.79 (d, J = 6.6 Hz, 3H) 61 66-72 -- HRMS-ESI .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 12.12 (d, J = (m/z) 0.6 Hz, 1H), 8.70 (d, 7.5
Hz, 1H), 8.00 (d, [M + H].sup.+ J = 5.2 Hz, 1H) 7.44-7.17 (m, 9H),
6.86 (dd, calcd for J = 5.3, 0.7 Hz, 1H), 4.94 (qd, J = 6.6, 4.3
Hz, C.sub.28H.sub.31N.sub.2O.sub.6, 1H), 4.60 (app td, J = 7.6, 5.4
Hz, 1H), 3.93 (s, 491.2177; 3H), 3.83 (ddd, J = 10.8, 7.7, 2.7 Hz,
1H), found, 3.40-3.22 (m, 3H), 2.91 (dd, J = 13.6, 6.1 491.2184 Hz,
1H), 2.79 (dd, J = 13.6, 9.4 Hz, 1H), 2.50- 2.37 (m, 1H), 1.92-1.79
(m, 1H), 1.45- 1.34 (m, 1H), 0.93 (d, J = 6.6 Hz, 3H) 62 138-141 --
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.13 (s, 1H),
(m/z) 8.54 (d, J = 8.1 Hz, 1H), 7.97 (d, J = 5.2 Hz, [M + H].sup.+
1H), 7.34-7.16 (m, 5H), 6.85 (d, J = 5.2 Hz, calcd for 1H), 5.16
(dq, J = 9.6, 6.4 Hz, 1H), 4.60 (dt, J =
C.sub.27H.sub.37N.sub.2O.sub.6, 9.5, 7.8 Hz, 1H), 4.04 (td, J =
10.5, 2.9 Hz, 485.2646; 1H), 3.92 (s, 3H), 3.60 (app t, J = 9.9 Hz,
1H), found, 3.40 (ddd, J = 9.6, 4.7, 2.4 Hz, 1H), 2.94 (dd,
485.2652 J = 15.6, 2.9 Hz, 1H), 2.83 (dd, J = 15.5, 10.5 Hz, 1H),
2.28 (dtt, J = 12.2, 4.9, 2.5 Hz, 1H), 1.95 (tt, J = 10.1, 3.8 Hz,
1H), 1.71-1.57 (m, 1H), 1.51-1.54 (m, 6H), 1.32-1.12 (m, 2H), 0.89
(d, J = 6.5 Hz, 3H), 0.88 (d, J = 6.5 Hz, 3H) 63 49-53 -- HRMS-ESI
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.13 (d, J = (m/z) 0.6
Hz, 1H), 8.69 (d, J = 7.6 Hz, 1H), 7.99 (d, [M + H].sup.+ J = 5.2
Hz, 1H), 6.87 (dd, J = 5.2, 0.7 Hz, 1H), calcd for 5.13 (qd, J =
6.6, 5.0 Hz, 1H), 4.65 (app td, J = C.sub.20H.sub.31N.sub.2O.sub.6,
7.95, 5.7 Hz, 1H), 3.94 (s, 3H), 3.86 (ddd, J = 395.2177; 10.9,
7.0, 2.7 Hz, 1H), 3.64 (dd, J = 11.1, 5.5 found, Hz, 1H), 3.58 (dd,
J = 11.0, 3.4 Hz, 1H), 3.52 395.2176 (ddd, J = 10.8, 8.1, 2.3 Hz,
1H), 2.48 (dddd, J = 14.4, 6.9, 5.8, 2.3 Hz, 1H), 1.95-1.82 (m,
1H), 1.66-1.31 (m, 7H), 1.24-1.10 (m, 2H), 0.89 (app dd, J = 6.6,
4.0 Hz, 6H) 64 -- -- HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 12.15 (s, 1H), (m/z) 8.60 (d, J = 8.1 Hz, 1H), 7.99 (d, J =
5.2 Hz, [M + H].sup.+ 1H), 7.32-7.25 (m, 2H), 7.23-7.15 (m, 3H),
calcd for 6.86 (d, J = 5.2 Hz, 1H), 5.11 (dq, J = 9.6, 6.4
C.sub.27H.sub.37N.sub.2O.sub.6, Hz, 1H), 4.62 (dt, J = 10.2, 7.8
Hz, 1H), 3.93 485.2646; (s, 3H), 3.71-3.53 (m, 3H), 2.83 (ddd, J =
found, 13.9, 8.8, 4.9 Hz, 1H), 2.59 (dt, J = 13.8, 8.3 485.2648 Hz,
1H), 2.49-2.36 (m, 1H), 1.82 (m, 4H), 1.32 (d, J = 6.5 Hz, 3H),
1.29-1.14 (m, 4H), 1.14-1.03 (m, 2H), 0.84 (t, J = 7.2 Hz, 3H)
.sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 171.50, 168.76, 155.30,
148.69, 141.77, 140.56, 130.47, 128.42, 128.41, 125.95, 109.45,
79.42, 75.20, 57.55, 56.06, 49.78, 43.34, 33.95, 32.20, 31.43,
27.82, 27.44, 23.31, 19.39, 13.80 65 -- (Thin HRMS-ESI .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 12.11 (d, J = Film) (m/z) 0.7 Hz,
1H), 8.58 (d, J = 8.1 Hz, 1H), 8.00 (d, 3362, [M + H].sup.+ J = 5.2
Hz, 1H), 6.87 (dd, J = 5.3, 0.6 Hz, 1H), 2952, calcd for 5.15 (dq,
J = 9.6, 6.4 Hz, 1H), 4.63 (dt, J = 2939,
C.sub.24H.sub.36N.sub.2O.sub.8, 9.6, 7.5 Hz, 1H), 4.30 (dd, J =
12.5, 2.6 Hz, 2871, 481.2544; 1H), 4.21 (dd, J = 12.5, 7.7 Hz, 1H),
3.94 (s, 1730, found, 3H), 3.90 (ddd, J = 10.5, 7.7, 2.5 Hz, 1H),
1649 481.2548 3.83-3.72 (m, 1H), 3.56 (ddd, J = 9.5, 4.6, 2.4 Hz,
1H), 2.60 (p, J = 7.0 Hz, 1H), 2.45- 2.35 (m, 1H), 1.99 (td, J =
10.2, 9.2, 4.0 Hz, 1H), 1.78 (dddd, J = 14.2, 10.7, 9.6, 2.4 Hz,
1H), 1.38 (d, J = 6.5 Hz, 3H), 1.36-1.22 (m, 6H), 1.19 (app dd, J =
7.0, 0.9 Hz, 6H), 0.90 (t, J = 7.2 Hz, 3H) 66 -- (Thin HRMS-ESI
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.13 (s, 1H), Film)
(m/z) 8.69 (d, J = 7.6 Hz, 1H), 7.99 (dd, J = 5.2, 1.0 3367, [M +
H].sup.+ Hz, 1H), 6.86 (d, J = 5.2 Hz, 1H), 5.18-5.07 2929, calcd
for (m, 1H), 4.65 (td, J = 7.9, 5.7 Hz, 1H), 3.94 2870,
C.sub.19H.sub.28N.sub.2O.sub.6, (d, J = 0.8 Hz, 3H), 3.86 (ddd, J =
10.3, 6.9, 1741, 381.202; 2.7 Hz, 1H), 3.67-3.47 (m, 3H), 2.48
(dtd, J = 1650 found, 16.7, 6.4, 2.3 Hz, 1H), 1.88 (dtd, J = 14.3,
381.2013 8.0, 2.5 Hz, 1H), 1.63 (ddp, J = 8.8, 5.5, 3.3, 2.8 Hz,
1H), 1.45 (dtd, J = 17.4, 8.9, 5.8 Hz, 1H), 1.34 (d, J = 6.6 Hz,
3H), 1.32-1.22 (m 5H), 0.90 (d, J = 7.2 Hz, 3H) 67 44-46 (Thin
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 12.14 (s, 1H),
Film) (m/z) 8.59 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 5.2 Hz, 3365,
[M].sup.+ 1H), 6.86 (d, J = 5.9 Hz, 1H), 5.19-5.07 (m, 2934, calcd
for 1H), 4.66-4.54 (m, 1H), 3.94 (s, 3H), 3.64- 1744,
C.sub.21H.sub.32N.sub.2O.sub.6, 3.55 (m, 1H), 3.53-3.42 (m, 2H),
2.45-2.33 1650, 408.2260; (m, 1H), 1.84-1.71 (m, 2H), 1.66-1.43 (m,
1529, found, 2H), 1.34 (d, J = 6.5 Hz, 3H), 1.32-1.09 (m, 1438,
408.2253 6H), 0.98 (t, J = 7.3 Hz, 3H), 0.89 (t, J = 6.8 1282 Hz,
3H) .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 171.51, 168.74,
155.26, 148.65, 140.56, 130.49, 109.41, 82.12, 75.27, 57.32, 56.05,
49.80, 43.62, 33.98, 27.96, 27.77, 23.37, 22.71, 19.40, 13.86,
10.83 68 77-79 (Thin HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 12.13 (s, 1H), Film) (m/z) 8.57 (d, J = 8.1 Hz, 1H), 8.00
(d, J = 5.2 Hz, 3366, [M].sup.+ 1H), 7.35-7.25 (m, 2H), 7.02-6.90
(m, 3H), 2933, calcd for 6.86 (d, J = 5.9 Hz, 1H), 5.26-5.15 (m,
1H),
1744, C.sub.26H.sub.34N.sub.2O.sub.7, 4.69-4.59 (m, 1H), 4.23-4.07
(m, 2H), 4.07- 1649, 486.2366; 3.98 (m, 1H), 3.93 (s, 3H),
3.93-3.86 (m, 1529, found, 1H), 3.66-3.58 (m, 1H), 2.41-2.31 (m,
1H), 1481, 486.2367 2.31-2.20 (m, 1H), 1.86-1.72 (m, 1H), 1.40 1242
(d, J = 6.5 Hz, 3H), 1.37-1.16 (m, 6H), 0.88 (t, J = 6.8 Hz, 3H)
.sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 171.48, 168.73, 158.34,
155.29, 148.68, 140.55, 130.47, 129.56, 121.20, 114.54, 109.45,
78.39, 74.94, 67.43, 60.43, 56.06, 49.97, 39.94, 34.13, 27.52,
27.24, 23.35, 19.32, 13.85 69 -- -- ESIMS -- m/z 264 ([M +
H].sup.+) 70 -- -- ESIMS -- m/z 306 ([M + H].sup.+) 71 -- -- ESIMS
-- m/z 320 ([M + H].sup.+) 72 -- -- ESIMS -- m/z 354 ([M +
H].sup.+) 73 -- -- ESIMS -- m/z 322 ([M + H].sup.+) 74 -- -- ESIMS
-- m/z 282 ([M + H].sup.+) 75 -- -- ESIMS -- m/z 310 ([M +
H].sup.+) 76 -- -- ESIMS -- m/z 338 ([M + H].sup.+) 77 -- -- ESIMS
-- m/z 386 ([M + H].sup.+) 78 -- -- ESIMS -- m/z 340 ([M +
H].sup.+) 79 -- -- ESIMS -- m/z 348 ([M + H].sup.+) 80 -- -- ESIMS
-- m/z 366 ([M + H].sup.+) 81 -- -- ESIMS -- m/z 340 ([M +
H].sup.+) 82 -- -- ESIMS -- m/z 334 ([M + H].sup.+) 83 -- -- ESIMS
-- m/z 244 ([M + H].sup.+) 84 -- -- ESIMS .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.73 (bs, 3H), m/z 334 7.32-7.22 (m, 2H), 7.17
(td, J = 7.1, 1.3 Hz, ([M + H].sup.+) 3H), 5.09 (dd, J = 9.7, 6.3
Hz, 1H), 4.07 (t, J = 8.8 Hz, 1H), 3.69-3.46 (m, 3H), 2.79 (dt, J =
13.9, 7.0 Hz, 1H), 2.64 (s, 1H), 2.53 (dt, J = 13.7, 8.2 Hz, 1H)
2.21-2.02 (m, 1H), 1.89- 1.64 (m, 5H), 1.32 (d, J = 6.4 Hz, 3H),
1.15 (dt, J = 13.4, 6.8 Hz, 3H), 1.10-1.01 (m, 1H), 0.82 (t, J =
7.2 Hz, 3H) 85 -- -- ESIMS -- m/z 330 ([M + H].sup.+) 86 -- --
ESIMS -- m/z 230 ([M + H].sup.+) 87 222-224 (Thin HRMS-ESI .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 8.62 (bs, 3H), Film) (m/z)
5.17-5.03 (m, 1H), 4.17-3.98 (m, 1H), 3.59- 3403, [M + H].sup.+
3.35 (m, 3H), 2.67-2.51 (m, 1H), 2.18- 2934, calcd for 1.97 (m,
1H), 1.77-1.66 (m, 1H), 1.65-1.38 1749, C.sub.14H.sub.28NO.sub.3,
(m, 2H), 1.34 (d, J = 6.4 Hz, 3H), 1.29-1.06 1515, 258.2069; (m,
6H), 0.95 (t, J = 7.2 Hz, 3H), 0.88 (t, J = 1380, found, 6.8 Hz,
3H) 1215 258.1988 .sup.13C NMR (75 MHz, CDCl.sub.3) .delta. 170.13,
82.25, 76.39, 57.65, 50.93, 43.84, 31.77, 28.08, 23.52, 23.04,
19.53, 14.02, 10.93 88 195-197 (Thin ESIMS .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 8.66 (bs, 3H), Film) m/z 336.4 7.31-7.21 (m,
2H), 6.99-6.83 (m, 3H), 5.25- 3396, ([M + H].sup.+) 5.09 (m, 1H),
4.23-3.95 (m, 3H), 3.91- 2933, 3.80 (m, 1H), 3.80-3.73 (m, 1H),
3.68-3.60 1748, (m, 1H), 2.61-2.48 (m, 1H), 2.28-2.04 (m, 1598,
2H), 1.38 (d, J = 6.3 Hz, 3H), 1.35-1.09 (m, 1496, 6H), 0.84 (t, J
= 6.7 Hz, 3H) 1242 89 -- -- ESIMS .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.33-7.23 (m, m/z 386 2H), 7.24-7.16 (m, 3H), 5.35 (d, J =
7.4 Hz, ([M + Na].sup.+) 1H), 5.14 (qd, J = 6.6, 3.8 Hz, 1H), 4.29
(td, J = 7.6, 5.1 Hz, 1H), 3.88 (ddd, J = 10.7, 7.6, 2.7 Hz, 1H),
3.59 (dd, J = 10.7, 4.4 Hz, 1H), 3.48-3.35 (m, 2H), 2.83 (dd, J =
13.5, 7.5 Hz, 1H), 2.72 (dd, J = 13.5, 8.6 Hz, 1H), 2.41- 2.31 (m,
1H), 1.86-1.67 (m, 2H), 1.45 (s, 9H), 1.24 (d, J = 6.7 Hz, 3H)
.sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 173.13, 155.13, 139.99,
129.14, 128.39, 126.11, 79.74, 72.99, 68.88, 66.67, 51.40, 45.74,
37.17, 32.74, 28.35, 21.11 90 -- -- ESIMS .sup.1H NMR (600 MHz,
CDCl.sub.3) .delta. 7.31 (t, J = 7.6 m/z 428 Hz, 2H), 7.23 (t, J =
7.4 Hz, 1H), 7.19 (d, J = ([M + Na].sup.+) 7.0 Hz, 2H), 5.24-5.08
(m, 2H), 4.23 (q, J = 8.5 Hz, 1H), 3.61-3.56 (m, 1H), 3.52 (td, J =
10.6, 1.9 Hz, 1H), 3.49-3.44 (m, 1H), 2.64 (dd, J = 15.8, 3.2 Hz,
1H), 2.52 (dd, J = 15.8, 6.8 Hz, 1H), 2.29 (ddd, J = 11.8, 7.2, 3.7
Hz, 1H), 2.22 (tdd, J = 10.0, 6.8, 3.2, Hz, 1H), 1.72- 1.60 (m,
1H), 1.59-1.48 (m, 4H), 1.46 (s, 9H), 1.30 (d, J = 6.5 Hz, 3H),
0.90 (t, J = 7.2 Hz, 3H) .sup.13C NMR (151 MHz, CDCl.sub.3) .delta.
172.57, 155.00, 139.74, 128.72, 128.55, 126.26, 80.87, 79.78,
75.15, 57.90, 51.19, 45.28, 35.01, 34.60, 31.92, 28.35, 20.48,
19.17, 13.92 91 -- -- ESIMS .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 7.31-7.26 (m, m/z 420 2H), 7.24-7.19 (m, 1H), 7.18-7.14 (m,
2H), ([M + H].sup.+) 5.13 (dq, J = 9.5, 6.5, 5.7 Hz, 2H), 4.21 (q,
J = 8.6 Hz, 1H), 3.59-3.50 (m, 1H), 3.50-3.38 (m, 2H), 2.60 (dd, J
= 15.8, 3.4 Hz, 1H), 2.49 (dd, J = 15.8, 6.6 Hz, 1H), 2.22 (dtdd, J
= 19.9, 10.0, 7.1, 3.7 Hz, 2H), 1.61-1.50 (m, 2H), 1.44 (s, 9H),
1.35-1.19 (m, 5H), 1.27 (d, J = 6.5 Hz, 3H), 0.87 (t, J = 7.0 Hz,
3H) .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 172.56, 155.00,
139.77, 128.70, 128.55, 126.25, 81.25, 79.78, 75.15, 57.89, 51.19,
45.37, 35.04, 34.59, 29.46, 28.35, 28.15, 22.51, 20.48, 14.02 92 --
-- ESIMS .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.36-7.24 (m,
m/z 454 3H), 7.25-7.19 (m, 4H), 7.19-7.15 (m, 3H), ([M + H].sup.+)
5.24-5.12 (m, 1H), 5.10 (d, J = 8.2 Hz, 1H), 4.21 (td, J = 9.3,
8.8, 7.0 Hz, 1H), 3.97 (td, J = 10.6, 2.5 Hz, 1H), 3.59 (t, J =
10.1 Hz, 1H), 3.38 (ddd, J = 9.7, 4.7, 2.4 Hz, 1H), 3.00 (dd, J =
15.9, 2.6 Hz, 1H), 2.84 (dd, J = 15.7, 10.9 Hz, 1H), 2.75 (dd, J =
15.9, 3.8 Hz, 1H), 2.65 (dd, J = 15.8, 6.3 Hz, 1H), 2.36 (tdd, J =
9.9, 6.3, 3.8 Hz, 1H), 2.21-2.10 (m, 1H), 1.50- 1.43 (m, 1H), 1.42
(s, 9H), 1.35 (d, J = 6.5 Hz, 3H) .sup.13C NMR (101 MHz,
CDCl.sub.3) .delta. 172.44, 154.96, 139.37, 138.61, 128.77, 128.70,
128.50, 128.44, 126.46, 126.21, 81.69, 79.78, 75.05, 59.21, 51.22,
45.77, 36.37, 35.17, 34.49, 28.33, 20.51 93 -- -- ESIMS .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.31-7.24 (m, m/z 444 2H), 7.22-7.13
(m, 3H), 5.21 (d, J = 8.2 Hz, ([M + Na].sup.+) 1H), 5.11 (dq, J =
9.6, 6.5 Hz, 1H), 4.28- 4.15 (m, 1H), 3.66 (td, J = 10.8, 2.2 Hz,
1H), 3.62-3.53 (m, 1H), 3.51-3.42 (m, 2H), 3.42- 3.32 (m, 1H), 3.30
(s, 3H), 2.60 (dd, J = 15.9, 3.4 Hz, 1H), 2.49 (dd, J = 15.9, 6.5
Hz, 1H), 2.32-2.17 (m, 2H), 1.98-1.90 (m, 1H), 1.90-1.79 (m, 1H),
1.65-1.50 (m, 1H), 1.43 (s, 9H), 1.27 (d, J = 6.5 Hz, 3H) .sup.13C
NMR (101 MHz, CDCl.sub.3) .delta. 172.34, 154.98, 139.61, 128.70,
128.54, 126.26, 79.73, 78.43, 75.14, 69.34, 58.74, 58.47, 51.11,
45.24, 34.72, 34.46, 30.04, 28.34, 20.43 94 -- -- ESIMS .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.18 (dd, J = m/z 382 8.5, 5.6 Hz,
2H), 6.97 (t, J = 8.7 Hz, 2H), 5.32 ([M + H].sup.+) (d, J = 7.3 Hz,
1H), 5.12 (qd, J = 6.7, 3.4 Hz, 1H), 4.29 (td, J = 7.7, 5.3 Hz,
1H), 3.91 (ddd, J = 10.8, 7.6, 2.7 Hz, 1H), 3.58 (dd, J = 10.7, 4.1
Hz, 1H), 3.45 (dd, J = 10.7, 2.4 Hz, 1H), 3.39 (ddd, J = 11.3, 7.4,
2.6 Hz, 1H), 2.81 (dd, J = 13.6, 7.8 Hz, 1H), 2.73 (dd, J = 13.7,
8.6 Hz, 1H), 2.45-2.27 (m, 1H), 1.73 (dtd, J = 15.9, 7.9, 4.7 Hz,
2H), 1.45 (s, 9H), 1.24 (d, J = 6.6 Hz, 3H) .sup.19F NMR (376 MHz,
CDCl.sub.3) .delta. -117.23 95 -- -- ESIMS .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.12 (dd, J = m/z 432 8.5, 5.4 Hz, 2H), 6.97
(t, J = 8.6 Hz, 2H), 5.19 ([M + Na].sup.+) (d, J = 8.2 Hz, 1H),
5.12 (dq, J = 9.4, 6.5 Hz, 1H), 4.21 (dt, J = 10.4, 7.8 Hz, 1H),
3.55 (dd, J = 11.3, 9.2 Hz, 1H), 3.50-3.43 (m, 1H), 3.38 (td, J =
10.4, 2.8 Hz, 1H), 2.61-2.54 (m, 1H), 2.49 (dd, J = 15.8, 6.5 Hz,
1H), 2.27 (ddd, J = 14.2, 7.5, 3.8 Hz, 1H), 2.14 (tdd, J = 9.9,
6.5, 3.4 Hz, 1H), 1.71-1.51 (m, 3H), 1.44 (s, 9H), 1.27 (d, J = 6.5
Hz, 3H), 0.94 (t, J = 7.2 Hz, 3H) .sup.19F NMR (376 MHz,
CDCl.sub.3) .delta. -116.83 96 -- -- ESIMS .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.12 (dd, J = m/z 460 8.5, 5.4 Hz, 2H), 6.97
(t, J = 8.6 Hz, 2H), 5.21 ([M + Na].sup.+) (d, J = 8.3 Hz, 1H),
5.12 (dq, J = 9.5, 6.5 Hz, 1H), 4.21 (dt, J = 10.6, 7.8 Hz, 1H),
3.55 (dd, J = 11.3, 9.2 Hz, 1H), 3.46 (td, J = 10.2, 2.9 Hz, 2H),
2.57 (dd, J = 15.9, 3.5 Hz, 1H), 2.48 (dd, J = 15.8, 6.6 Hz, 1H),
2.25 (ddd, J = 14.2, 7.3, 3.5 Hz, 1H), 2.14 (ddt, J = 13.0, 6.4,
3.6 Hz, 1H), 1.65-1.49 (m, 3H), 1.45-1.40 (m, 1H), 1.44 (s, 9H),
1.37-1.27 (m, 3H), 1.26 (d, J = 6.5 Hz, 3H), 0.87 (t, J = 7.0 Hz,
3H) .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -116.82 97 -- --
ESIMS .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.30-7.23 (m, m/z
508 2H), 7.19 (t, J = 7.3 Hz, 1H), 7.15-7.11 (m, ([M + Na].sup.+)
2H), 6.99 (dd, J = 8.5, 5.5 Hz, 2H), 6.91 (t, J = 8.7 Hz, 2H),
5.23-5.15 (m, 1H), 5.09 (dq, J = 9.5, 6.5 Hz, 1H), 4.23 (dt, J =
10.5, 7.8 Hz, 1H), 3.65-3.45 (m, 3H), 2.77 (ddd, J = 13.8, 9.0, 4.7
Hz, 1H), 2.59-2.49 (m, 1H), 2.44 (td, J = 15.8, 14.9, 5.1 Hz, 2H),
2.30 (ddd, J = 14.6, 7.6, 3.6 Hz, 1H), 2.14 (tdd, J = 9.9, 6.3, 3.6
Hz, 1H), 1.98-1.77 (m, 2H), 1.67-1.55 (m, 1H), 1.44 (s, 9H), 1.27
(d, J = 6.5 Hz, 3H) .sup.19F NMR (376 MHz, CDCl.sub.3) .delta.
-116.69 98 -- -- ESIMS .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
7.14 (dd, J = m/z 462 8.4, 5.5 Hz, 2H), 6.97 (t, J = 8.6 Hz, 2H),
5.17 ([M + Na].sup.+) (d, J = 8.2 Hz, 1H), 5.10 (dq, J = 9.5, 6.5
Hz, 1H), 4.22 (dt, J = 10.4, 7.8 Hz, 1H), 3.65 (td, J = 10.6, 2.6
Hz, 1H), 3.58 (dd, J = 11.0, 9.3 Hz, 1H), 3.45 (dtd, J = 14.2, 7.1,
6.4, 2.7 Hz, 2H), 3.40-3.33 (m, 1H), 3.31 (s, 3H), 2.58 (dd, J =
16.1, 3.6 Hz, 1H), 2.48 (dd, J = 16.0, 6.4 Hz, 1H), 2.27 (ddd, J =
14.3, 7.6, 4.0 Hz, 1H), 2.18 (tdd, J = 9.9, 6.4, 3.4 Hz, 1H), 1.97-
1.79 (m, 2H), 1.63-1.52 (m, 1H), 1.44 (s, 9H), 1.27 (d, J = 6.5 Hz,
3H) .sup.19F NMR (376 MHz, CDCl.sub.3) .delta. -116.82 99 -- --
ESIMS .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 7.32-7.23 (m, m/z
471 2H), 7.22-7.14 (m, 3H), 5.22 (d, J = 8.3 Hz, ([M + Na].sup.+)
1H), 5.04 (dq, J = 9.5, 6.5 Hz, 1H), 4.29- 4.15 (m, 1H), 3.61-3.46
(m, 3H), 2.80 (ddd, J = 13.7, 8.9, 4.7 Hz, 1H), 2.63-2.50 (m, 1H),
2.34-2.23 (m, 1H), 1.87-1.69 (m, 3H), 1.67-1.56 (m, 1H), 1.44 (s,
9H), 1.40-1.14 (m, 6H), 1.00-0.88 (m, 2H), 0.81 (d, J = 6.6 Hz,
3H), 0.78 (d, J = 6.6 Hz, 3H) .sup.13C NMR (101 MHz, CDCl.sub.3)
.delta. 172.61, 155.02, 141.79, 128.43, 128.40, 125.93, 79.68,
79.00, 74.63, 57.53, 51.14, 43.29, 34.60, 34.01, 32.15, 31.39,
28.60, 28.36, 25.76, 22.44, 22.22, 19.37 100 39-44 -- ESIMS .sup.1H
NMR (400 MHz, CDCl.sub.3) .delta. 7.17-7.09 (m, m/z 489 2H),
7.00-6.91 (m, 2H), 5.20 (d, J = 8.3 Hz, ([M + Na].sup.+) 1H), 5.04
(dq, J = 9.6, 6.5 Hz, 1H), 4.28- 4.16 (m, 1H), 3.60-3.44 (m, 3H),
2.77 (ddd, J = 13.6, 8.7, 4.6 Hz, 1H), 2.55 (app dt, J = 13.9, 8.2
Hz, 1H), 2.29 (ddd, J = 14.1, 7.8, 3.8 Hz, 1H), 1.87-1.65 (m, 3H),
1.67-1.52 (m, 1H), 1.44 (s, 9H), 1.40-1.23 (m, 4H), 1.19 (tdd, J =
9.9, 6.2, 3.7 Hz, 2H), 1.01-0.85 (m, 2H), 0.81 (d, J = 6.6 Hz, 3H),
0.79 (d, J = 6.6
Hz, 3H) 101 -- -- ESIMS .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
7.44-7.15 (m, m/z 440 9H), 5.31 (d, J = 7.2 Hz, 1H), 4.87 (qd, J =
([M + H].sup.+) 6.6, 4.4 Hz, 1H), 4.21 (app td, J = 7.5, 5.2 Hz,
1H), 3.76 (ddd, J = 10.9, 7.9, 2.7 Hz, 1H), 3.32-3.17 (m, 3H), 2.87
(dd, J = 13.6, 6.0 Hz, 1H), 2.74 (dd, J = 13.6, 9.5 Hz, 1H), 2.36-
2.24 (m, 1H), 1.73-1.60 (m, 1H), 1.45- 1.32 (m, 10H), 0.90 (d, J =
6.6 Hz, 3H) .sup.13C NMR (101 MHz, CDCl.sub.3) .delta. 173.05,
155.09, 142.06, 141.70, 137.21, 130.78, 130.18, 129.03, 128.21,
127.31, 126.99, 126.32, 79.68, 73.49, 67.98, 66.03, 51.27, 43.83,
34.44, 32.50, 28.36, 20.38 102 41-44 -- ESIMS .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 7.30-7.19 (m, m/z 456 5H), 5.16-5.04 (m, 2H),
4.26-4.15 (m, 1H), ([M + Na].sup.+) 4.01 (td, J = 10.6, 3.1 Hz,
1H), 3.59-3.48 (m, 1H), 3.39-3.30 (m, 1H), 2.98-2.86 (m, 1H), 2.81
(dd, J = 15.5, 10.4 Hz, 1H), 2.21-2.10 (m, 1H), 1.96-1.84 (m, 1H),
1.51-1.32 (m, 16H), 1.30-1.09 (m, 2H), 0.88 (d, J = 6.5 Hz, 3H),
0.86 (d, J = 6.5 Hz, 3H) 103 110-112 -- ESIMS .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 5.29 (d, J = 7.5 m/z 344 Hz, 1H), 5.06 (qs, J =
6.6, 5.2 Hz, 1H), 4.26 ([M + H].sup.+) (app q, J = 7.1 Hz, 1H),
3.79 (ddd, J = 11.0, 7.1, 2.7 Hz, 1H), 3.59 (dd, J = 11.0, 5.6 Hz,
1H), 3.53 (dd, J = 11.0, 3.5 Hz, 1H), 3.44 (ddd, J = 10.7, 8.0, 2.4
Hz, 1H), 2.41-2.29 (m, 1H), 1.75-1.29 (m, 17H), 1.20-1.09 (m, 2H),
0.87 (app dd, J = 6.6, 4.2 Hz, 6H) 104 -- -- ESIMS .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. 7.31-7.24 (m, m/z 456 2H), 7.18 (ddt, J =
7.0, 3.2, 1.4 Hz, 3H), 5.19 ([M + Na].sup.+) (d, J = 8.3 Hz, 1H),
5.05 (dq, J = 9.6, 6.4 Hz, 1H), 4.22 (dt, J = 10.2, 7.7 Hz, 1H),
3.63- 3.44 (m, 3H), 2.81 (ddd, J = 14.0, 8.9, 5.2 Hz, 1H), 2.56
(dt, J = 13.9, 8.3 Hz, 1H), 2.20 (ddd, J = 14.3, 7.5, 3.4 Hz, 1H),
1.87-1.69 (m, 3H), 1.67-1.53 (m, 1H), 1.44 (s, 9H), 1.29 (d, J =
6.5 Hz, 3H), 1.23-1.13 (m, 3H), 1.12- 1.02 (m, 2H), 0.92-0.86 (m,
1H), 0.83 (t, J = 7.2 Hz, 3H) .sup.13C NMR (101 MHz, CDCl.sub.3)
.delta. 172.63, 155.02, 141.82, 128.39, 125.93, 79.72, 79.37,
74.76, 57.53, 51.13, 43.37, 34.65, 32.25, 31.44, 28.35, 27.83,
27.46, 23.30, 19.39, 13.80 105 -- -- ESIMS .sup.1H NMR (400 MHz,
CDCl.sub.3) .delta. 5.17 (d, J = 8.1 m/z 430 Hz, 1H), 5.10 (dq, J =
9.6, 6.4 Hz, 1H), 4.32- ([M + H].sup.+) 4.15 (m, 3H), 3.86 (ddd, J
= 10.7, 7.8, 2.6 Hz, 1H), 3.67 (t, J = 10.1 Hz, 1H), 3.49 (ddd, J =
9.3, 4.3, 2.4 Hz, 1H), 2.65-2.53 (m, 1H), 2.32-2.21 (m, 1H),
1.98-1.88 (m, 1H), 1.76- 1.68 (m, 1H), 1.44 (s, 9H), 1.34 (d, J =
6.5 Hz, 3H), 1.31-1.22 (m, 6H), 1.18 (app dd, J = 7.0, 1.1 Hz, 6H),
0.89 (t, J = 7.2 Hz, 3H) .sup.13C NMR (101 MHz, CDCl.sub.3) .delta.
176.87, 172.49, 154.95, 79.79, 77.74, 74.39, 63.12, 51.19, 40.38,
33.96, 31.58, 28.32, 27.52, 23.28, 22.64, 19.24, 18.96, 18.89,
14.11, 13.80 106 -- -- ESIMS .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. 5.29 (d, J = 7.5 m/z 330 Hz, 1H), 5.05 (qd, J = 6.6, 5.2
Hz, 1H), 4.26 ([M + H].sup.+) (td, J = 7.7, 5.6 Hz, 1H), 3.79 (ddd,
J = 11.0, 7.1, 2.8 Hz, 1H), 3.65-3.50 (m, 2H), 3.44 (ddd, J = 10.7,
8.1, 2.4 Hz, 1H), 2.35 (dt, J = 14.7, 6.4 Hz, 1H), 1.69 (dtt, J =
14.2, 5.2, 2.7 Hz, 1H), 1.60 (dtd, J = 9.4, 5.6, 3.4 Hz, 1H), 1.44
(s, 9H), 1.41-1.35 (m, 1H), 1.30 (d, J = 6.7 Hz, 3H), 1.29-1.21 (m,
5H), 0.89 (t, J = 7.0 Hz, 3H) .sup.13C NMR (101 MHz, CDCl.sub.3)
.delta. 173.03, 155.09, 79.68, 74.21, 69.67, 65.81, 51.34, 42.95,
33.04, 30.32, 29.45, 28.33, 22.86, 20.72, 14.00 107 -- (Thin
HRMS-ESI .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. 5.26-5.14 (m,
Film) (m/z) 1H), 5.12-5.00 (m, 1H), 4.26-4.16 (m, 1H), 3360, [M +
Na].sup.+ 3.55-3.46 (m, 1H), 3.46-3.37 (m, 2H), 2.31- 2933, calcd
for 2.19 (m, 1H), 1.80-1.69 (m, 1H), 1.65- 1715,
C.sub.19H.sub.35NNaO.sub.5, 1.43 (m, 3H), 1.44 (s, 9H), 1.31 (d, J
= 6.5 Hz, 1500, 380.2413; 3H), 1.29-1.09 (m, 6H), 0.96 (t, J = 7.3
Hz, 1367, found, 3H), 0.89 (t, J = 6.8 Hz, 3H) 1166 380.2330
.sup.13C NMR (75 MHz, CDCl.sub.3) .delta. 172.76, 155.15, 82.12,
79.78, 74.95, 57.45, 51.32, 43.80, 34.80, 28.50, 28.14, 27.93,
23.53, 22.83, 19.55, 14.01, 10.98 108 -- (Thin HRMS-ESI .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. 7.35-7.23 (m, Film) (m/z) 2H),
7.01-6.87 (m, 3H), 5.23(d, J = 7.8 Hz, 3357, [M].sup.+ 1H),
5.20-5.09 (m, 1H), 4.30-4.18 (m, 1H), 2932, calcd for 4.18-4.03 (m,
2H), 4.03-3.92 (m, 1H), 3.85- 1711, C.sub.24H.sub.37NO.sub.6, 3.74
(m, 1H), 3.58-3.50 (m, 1H), 2.29- 1497, 435.2621; 2.11 (m, 2H),
1.69-1.52 (m, 1H), 1.43 (s, 1366, found, 9H), 1.36 (d, J = 6.5 Hz,
3H), 1.41-1.12 (m, 1243, 435.2621 6H), 0.87 (t, J = 6.8 Hz, 3H)
1162 .sup.13C NMR (75 MHz, CDCl.sub.3) .delta. 172.56, 158.37,
154.96, 129.51, 121.14, 114.54, 79.62, 78.18, 74.40, 67.35, 60.20,
51.28, 39.92, 34.67, 28.32, 27.53, 27.25, 23.31, 19.29, 13.82
*.sup.1H NMR were run at 400 MHz unless noted otherwise. *.sup.13C
NMR were run at 101 MHz unless noted otherwise. *.sup.19F NMR were
run at 376 MHz unless noted otherwise.
TABLE-US-00003 TABLE 3 Biological Testing Rating Scale Rating Table
for Fungal Pathogens % Control Rating >70 A .ltoreq.70 B Not
Tested C
TABLE-US-00004 TABLE 4 Biological Activity-PUCCRT and SEPTTR
Disease Control in High and Low Volume Applications Low Volume High
Volume (121.5 g/H*) (100 ppm*) *Cmpd. PUCCRT* SEPTTR* PUCCRT*
SEPTTR* No. 1 DP* 3 DC* 1 DP* 3 DC* 1 DP* 3 DC* 1 DP* 3 DC* 1 A A A
A C C C C 2 A A A A C C C C 3 A A A A C C C C 4 A A A A C C C C 5 A
A A B C C C C 6 A A A A C C C C 7 A A A A C C C C 8 A A A B C C C C
9 A A A A C C C C 10 A A A A C C C C 11 A A A B C C C C 12 A A A A
C C C C 13 A A A A C C C C 14 A A A B C C C C 15 A A A A C C C C 16
A A B B C C C C 17 A A A A A A A A 18 A A A A C C C C 19 A A A A C
C C C 20 A A A A C C C C 21 A A A B C C C C 22 A A A A C C C C 23 A
A A A C C C C 24 A A A A C C C C 25 A A B B C C C C 26 A A A A C C
C C 27 A A A A C C C C 28 A A A A C C C C 29 A A A A C C C C 30 A A
A A C C C C 31 A A A A C C C C 32 A A A A C C C C 33 C C C C C C C
C 34 A A B B C C C C 35 A A A A C C C C 36 A A A B C C C C 37 A A A
A C C C C 38 A A A A C C C C 39 A A A B C C C C 40 A A A A C C C C
41 A A A A C C C C 42 A A A A C C C C 43 A A A A A A A A 44 A A A A
C C C C 45 A A A A C C C C 46 A A A B C C C C 47 A A A A C C C C 48
A A B B C C C C 49 C C C C C C C C 50 C C C C A A A A 51 C C C C C
C C C 52 C C C C C C C C 53 C C C C C C C C 54 C C C C C C C C 55 C
C C C A A A A 56 C C C C A A B A 57 C C C C A B A A 58 C C C C C C
C C 59 C C C C A A A A 60 C C C C C C C C 61 C C C C C C C C 62 C C
C C C C C C 63 C C C C C C C C 64 C C C C A A A A 65 C C C C C C C
C 66 C C C C C C C C 67 C C C C A A A B 68 C C C C A A A B *Cmpd.
No.--Compound Number *PUCCRT--Wheat Brown Rust (Puccinia tritcina)
*SEPTTR--Wheat Leaf Blotch (Zymoseptoria tritici) *1 DP--1 Day
Protectant *3 DC--3 Day Curative *g/H--Grams Per Hectare
*ppm--Parts Per Million
TABLE-US-00005 TABLE 5 Biological Activity - Disease Control at 100
ppm *Cmpd. ALTESO* CERCBE* COLLLA* ERYSCI* ERYSGH* No. 1DP* 2 B A A
B B 3 B A A B B 17 B A A B B *Cmpd. No. - Compound Number *ALTESO -
Tomato Earyl Blight (Alternaria solani) *CERCBE - Leaf Spot of
Sugar Beets (Cercospora beticola) *COLLLA - Cucumber Anthracnose
(Glomerella lagenarium; Anamorph: Colletotricum lagenarium) *ERYSCI
- Powdery Mildew of Cucumber (Erysiphe cichoracearum) *ERYSGH -
Barley Powdery Mildew (Blumeria graminis f. sp. hordei; Synonym:
Erysiphe graminis f. sp. hordei) *1DP - 1 Day Protectant
TABLE-US-00006 TABLE 6 Biological Activity - Disease Control at 100
ppm *Cmpd. LEPTNO* PYRIOR* RHYNSE* UNCINE* VENTIN* No. 1DP 2 A A A
C C 3 A A B C C 17 A A B A B *Cmpd. No. - Compound Number *LEPTNO -
Wheat Glume Blotch (Leptosphaeria nodorum) *PYRIOR - Rice Blast
(Magnaporthe grisea) *RHYNSE - Barley Scald (Rhyncosporium secalis)
*UNCINE - Grape Powdery Mildew (Uncinula necator) *VENTIN - Apple
Scab (Venturia inaequalis) *1DP - 1 Day Protectant
TABLE-US-00007 TABLE 7 Biological Activity - Disease Control at 25
ppm *Cmpd. PHAKPA* No. 1DP* 3DC* 17 A A 43 A A *Cmpd. No. -
Compound Number *PHAKPA - Asian Soybean Rust (Phakopsora
pachyrhizi) *1DP - 1 Day Protectant *3DC - 3 Day Curative
* * * * *