U.S. patent number RE33,719 [Application Number 07/352,847] was granted by the patent office on 1991-10-15 for sweetened edible formulations.
This patent grant is currently assigned to Biospherics Incorporated. Invention is credited to Gilbert V. Levin.
United States Patent |
RE33,719 |
Levin |
* October 15, 1991 |
Sweetened edible formulations
Abstract
This disclosure is concerned with a variety of methods for
preparing various L-hexose monosaccharides and organoleptic testing
in regard to the sweetness of these saccharides. The disclosure is
further concerned with the use of these L-hexose monosaccharides as
sweetening agents in a wide variety of foodstuffs and other edible
formulations. The L-hexose monosaccharides disclosed include
L-glucose, L-allose, L-fructose, L-gulose, L-galactose, L-altrose,
L-idose, L-talose, L-tagatose and L-psicose.
Inventors: |
Levin; Gilbert V. (Annapolis,
MD) |
Assignee: |
Biospherics Incorporated
(Beltsville, MD)
|
[*] Notice: |
The portion of the term of this patent
subsequent to October 15, 2005 has been disclaimed. |
Family
ID: |
37773583 |
Appl.
No.: |
07/352,847 |
Filed: |
May 16, 1989 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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683157 |
May 4, 1976 |
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106896 |
Jan 15, 1971 |
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672457 |
Oct 3, 1967 |
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Reissue of: |
838211 |
Sep 30, 1977 |
04262032 |
Apr 14, 1981 |
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Current U.S.
Class: |
426/658; 426/804;
514/23 |
Current CPC
Class: |
A23L
2/60 (20130101); A23G 3/346 (20130101); C07H
13/04 (20130101); C07C 205/15 (20130101); C07H
11/00 (20130101); A21D 2/181 (20130101); C12G
3/06 (20130101); A23L 27/38 (20160801); C07H
3/02 (20130101); A61Q 11/00 (20130101); A61K
8/60 (20130101); A23G 3/346 (20130101); A23G
2200/06 (20130101); A23G 2200/06 (20130101); Y10S
426/804 (20130101) |
Current International
Class: |
A23G
3/34 (20060101); A23L 1/236 (20060101); A21D
2/00 (20060101); A21D 2/18 (20060101); C07H
3/02 (20060101); C12G 3/06 (20060101); C12G
3/00 (20060101); C07H 3/00 (20060101); A23L
001/09 () |
Field of
Search: |
;426/658,804 ;424/361
;536/1 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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1150999 |
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Aug 1983 |
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CA |
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3414382 |
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Nov 1984 |
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DE |
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1566821 |
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May 1980 |
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GB |
|
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|
Primary Examiner: Cintins; Marianne
Attorney, Agent or Firm: Bryan, Cave, McPheeters &
McRoberts
Parent Case Text
This application is a continuation-in-part of application Ser. No.
683,157, filed May 4, 1976; now abandoned which was a continuation
of application Ser. No. 106,896, filed Jan. 15, 1971 (now
abandoned); which was a continuation of application Ser. No.
672,457, filed Oct. 3, 1967 (now abandoned).
Claims
I claim:
1. A process for the preparation of a sweetened edible formulation
in which the sweetening agent is non-calorific .Iadd.in a human
.Iaddend.and less susceptible to spoilage due to the growth of
microorganisms which comprises the step of mixing a food stuff with
an amount sufficient to sweeten said food stuff of an L-hexose
monosaccharide selected from the group consisting of L-glucose,
L-allose, L-fructose, L-gulose, L-galactose, L-altrose, L-idose,
L-talose, L-tagatose and L-psicose as a sweetening agent.
2. A process as defined in claim 1 wherein said L-hexose
monosaccharide is L-glucose.
3. A process as defined in claim 1 wherein said L-hexose
monosaccharide is L-allose.
4. A process as defined in claim 1 wherein said L-hexose
monosaccharide is L-fructose.
5. A process as defined in claim 1 wherein said L-hexose
monosaccharide is L-gulose.
6. A process as defined in claim 1 wherein said L-hexose
monosaccharide is L-galactose.
7. A process as defined in claim 1 wherein said L-hexose
monosaccharide is L-altrose.
8. A process as defined in claim 1 wherein said L-hexose
monosaccharide is L-idose.
9. A process as defined in claim 1 wherein said L-hexose
monosaccharide is L-talose.
10. A process as defined in claim 1 wherein said L-hexose
monosaccharide is L-tagatose.
11. A process as defined in claim 1 wherein said L-hexose
monosaccharide is L-psicose. .Iadd.
12. The process of claim 1 wherein the foodstuff is selected from
the group consisting of fruits, vegetables, meat products, milk
products, egg products, pickles, relishes, ice creams, sherberts,
ices, ice milk products, bakery products, icings, confections,
confection toppings, syrups, flavors, cake mixes, pastry mixes,
beverages, dietary-type foods, medicinal preparations, tobacco
products, and gum adhesives. .Iaddend. .Iadd.13. The process of
claim 12 wherein the foodstuff is a meat product selected from the
group consisting of bacon and ham. .Iaddend. .Iadd.14. The process
of claim 12 wherein the foodstuff is a milk product selected from
the group consisting of chocolate dairy drinks. .Iaddend. .Iadd.15.
The process of claim 12 wherein the foodstuff is an egg product
selected from the group consisting of egg nogs, custards, angel
food mixes, and salad dressings. .Iaddend. .Iadd.16. The process of
claim 12 wherein the foodstuff is a beverage selected from the
group consisting of fruit juices, vegetable juices, carbonated soft
drinks, fruit aids, and wines. .Iaddend. .Iadd.17. The process of
claim 16 wherein the beverage is a carbonated soft drink. .Iaddend.
.Iadd.18. The process of claim 12 wherein the foodstuff is a
medicinal preparation selected from the group consisting of cough
syrup, pastes, powders, foams and denture-retaining adhesives,
mouthwash, and oral antiseptic liquid. .Iaddend.
Description
This invention is concerned with foodstuffs and other edible
formulations containing sweetening agents which are of particular
value in the treatment or prevention of obesity or other conditions
in which the normal function of the body in regard to carbohydrate
metabolism is impaired.
More particularly, this invention is concerned with the preparation
of foodstuffs having properties such as appetizing appearance,
texture and taste, which are similar to those associated with the
common sugar sweetening agents. However, the foodstuffs and other
edible formulations prepared according to this invention will not
have the deleterious effects, in some people, that are associated
with those foodstuffs prepared with the common sugar sweetening
agents. Thus, this invention is concerned with the sweetening of
foodstuffs and other edible formulations with novel sweetening
agents comprising the L-hexose monosaccharides. These sweetening
agents are unique in that their physical properties are similar to
those of the natural sugars used as sweetening agents, but as
opposed to the common sugars, these compounds are either not
metabolized by the body or are metabolized to such a small extent,
that they do not impart to the body the detrimental effects that
some people have due to the improper metabolization of the common
sugar sweetening agents.
It is well known that the intake of certain carbohydrates, and in
particular D-glucose, and certain oligosaccharides, particularly
those converted to D-glucose, such as sucrose, must be carefully
regulated or entirely restricted in people suffering from
conditions such as diabetes mellitus and similar conditions wherein
the function of the pancreas is impaired in regard to carbohydrate
metabolism. A similar situation also exists in persons in the
treatment or prevention of obesity.
Numerous proposals have been made in the prior art to provide a
suitable means for the sweetening of foods for persons who must
restrict their intake of metabolizable carbohydrates. However,
these prior art methods are definitely deficient in several
respects and hence, cannot be considered as ideal non-nutritive
sweetening agents. For example, the commonly used artificial
sweetening agents, such as saccharin, cyclamates and mixtures leave
a bitter and objectional aftertaste, after foods sweetened with
these have been eaten. Likewise, since they are used in very minute
amounts, due to their high degree of sweetness, various bulking
agents must be added to serve as a carrier and, in some cases,
replace the bulk normally supplied by the replaced sugar. The use
of bulking agents is particularly necessary in situations wherein
solid foods, such as breads, cakes, cookies, cake-icing, solid and
semi-solid candles and chewing gum are to be prepared, since it is
practically impossible to prepare this type of food with a
wholesome and appetizing appearance without the use of some bulking
agent to replace the volume of normal sugar, which is not required
by the use of artificial sweetness. However, the use of various
bulking agents presents difficulties in that those most effective
in replacing the bulk of the normal sugar are for the most part
based upon carbohydrates, which are metabolized by the body and,
hence, have some nutritive value.
According to the present invention, the use of certain L-hexose
monosaccharides as sweetening agents alleviates the problems of the
prior art sweetening agents.
These novel sweetening agents have no bitter and objectional
aftertaste, and, further, since they have practically the same
physical properties appearance as the normal sugars used as
sweetening agents, the problem of the use of carriers, and bulking
agents to improve the appearance of foodstuffs prepared therefrom
is negated.
The ability of the subject L-hexoses to function as sweetening
agents is unique, in view of reports in the prior art as to their
property of being non-sweet and having a salty taste.
Due to the fact that these L-hexose monosaccharides are either not
metabolized by the body or they are metabolized to such a small
extent, they will have little or no effect upon the normal body
functions. Consequently, these new sweetening agents may ideally be
used in foodstuffs and other edible formulations designed for
persons whose metabolizable carbohydrate intake must be restricted
because of conditions such as diabetes mellitus or obesity.
Another outstanding feature of the use of the subject L-hexose
sweetening agents, is that formulations prepared using them as
sweetening agents are less susceptible to spoilage due to the
growth of various microorganisms than those prepared with the
conventional saccharide sweetening agents. For example, one large
problem encountered with the use of formulations such as syrups,
prepared from conventional saccharide sweetener such as in the soft
drink industry, is the decomposition due to bacterial growth. Since
the L-hexose saccharide sweetening agents of the present invention
provide little or no nutrient value for the various microorganisms,
their growth and, hence, the corresponding spoilage of these
formulations is drastically reduced.
Other advantages of the subject L-hexose sweetening agents are that
they are non-calorific and are believed to be non-carcinogenic.
Thus, they are suitable substitutes for sugar for persons on a
reducing diet, and they probably do not possess the carcinogenic
disadvantages associated with saccharin and cyclomates.
The term L-hexose monosaccharides as used herein is used within the
meaning of the standard terminology of carbohydrate chemists. Thus,
for example, one particularly effective sweetening agent according
to this invention is L-glucose, which is a stereoisomer of the
widely known sweetening agent D-glucose. The D- and L- prefixes are
used to denote the configuration of the hexose structure according
to the universally accepted Fisher system of nomenclature as
modified by Rosanoff. This may be further exemplified by reference
to the following structural formulas: ##STR1##
As may be ascertained from these formulas, these two compounds are
mirror images of one another. The prefixes of D- and L- are not to
be confused with d- and l-, which are used to denote the direction
of optical rotation, i.e., d(dextro-) or l(levo-). This is
discussed more fully below.
As is common in the art, the term hexose is inclusive to those six
carbon sugars or monosaccharides, wherein the carbonyl group is
either in the aldehyde form (aldoses) or the keto form (ketoses)
and monosaccharide refers to the simple or uncombined sugar.
Typical examples of these aldoses or aldohexoses are L-talose,
L-galatose and L-allose, while typical examples of these ketoses or
ketohexoses are L-tagatose and L-psicose.
A better understanding of the products and processes of this
invention may be obtained from the examples given below, which
disclose the best mode presently contemplated by the inventor of
carrying out this invention.
EXAMPLE 1
L-Glucose
A solution of 50 grams of .beta.-L-arbinose and 180 ml. of
nitromethane in 100 ml. of absolute methanol was heated in a
3-neck, 1-liter flask with a solution of 10.5 grams of 350 ml. of
absolute methanol. The reaction mixture was protected from
moisture, refluxed and stirred for 18-20 hours. The resulting
precipitate of sodium aci-nitroalcohols was collected by filtration
and washed with cold methanol and then with petroleum ether. The
moist salts were then dissolved in 400 ml. of cold (0.degree. C.)
water and the solution immediately deionized by passage through a
column containing 400 ml. of Dowex-50(H+) resin. The effluent and
washings were concentrated at reduced pressure with several
portions of absolute ethanol to remove residual water. The
resulting crystals were filtered with the aid of cold ethanol and
the filtrate reworked to provide two additional crops of crystals.
This yielded approximately 55 grams of crude mixed nitroalcohols.
This crude product was separated by fractional crystallization from
ethanol. The less soluble fraction was 1-deoxy-1 -nitro-L-mannitol,
m.p. 133.degree.-134.degree. C. (18 gr.) and the more soluble
fraction 1-deoxy-1-nitro-L-glucitol, m.p. 104.degree.-106.degree.
C. (15 gr.).
A solution of 5 grams of 1-deoxy-1-nitro-L-glucitol dissolved in 15
ml. of 2N sodium hydroxide was added dropwise to a stirred solution
of 7.5 ml. of sulfuric acid in 9 ml. of water at room temperature.
After dilution with 200 ml. of water, the solution was neutralized
to Congo red indicator with warm barium hydroxide solution and the
remaining sulfate ion precipitated with barium acetate solution.
The barium sulfate was removed by filtration and the filtrate
de-ionized by passage through 50 ml. of Dowex-50(H+) resin. The
effluent and washings were concentrated at reduced pressure to a
syrup. This syrup was diluted with a few drops of ethanol and
allowed to crystallize. The resulting .beta.-L-glucose was filtered
with the aid of ethanol; yield 2.5 grams, mp
146.degree.-147.degree. C.
EXAMPLE 2
.beta.-L-Allose
A solution of 13 grams of L-allono-1,4-lactone [Austin and Humdles,
JACS 56 1152 (1934), Hudson et al, ibid 56 1248 (1934)] in 100 ml.
of water was cooled at 0.degree. C. in an ice-salt mixture. This
was reduced by adding to the lactone solution small amounts of a
2.5% sodium amalgam. During the reduction, the reaction mixture was
maintained on the acid side of Congo red (pH 5) by the intermittent
addition of 20% sulfuric acid, as needed. The reaction mixture was
agitated vigorously during this step to prevent the formation of
local zones of alkalinity. Periodically, small aliquots of the
reaction mixture were withdrawn and tested for reducing sugar
content. Approximately 400 grams of the 2.5% sodium amalgram were
needed to produce the maximum quantity of reducing sugar. After the
addition of the sodium amalgram, the aqueous phase was decanted
from the mercury, filtered and hot ethanol added with stirring to
bring the final concentration to 85%. The precipitated sodium
sulfate was removed by filtration and the filtrate concentrated to
about 50 ml. at reduced pressure and at a temperature less than
45.degree. C. This filtrate was poured through a pad of activated
carbon and then titrated with a one-half saturated solution of
barium hydroxide using phenolphthalein as an indicator. The
reaction mixture was poured into ten volumes of hot, absolute
ethanol and the resulting barium L-allonate, which is insoluble in
93% ethanol, was filtered. The filtrate was evaporated under
reduced pressure to a thin syrup and allowed to crystallize.
Crystals were separated by filtration, the filtrate and washings
were concentrated to a thin syrup and an additional crop of
.beta.-L-allose was obtained upon storage in a desicator. This gave
a yield of about 70%. Recrystallization was effected from hot 93%
ethanol to yield pure crystals, m.p. 128.degree.-129.degree. C.
EXAMPLE 3
.beta.-L-Fructose Hemihydrate
1-Deoxy-1-diazo-keto-L-fructose tetracetate
A solution of 14 grams of tetra-O-acetyl-L-arabinoyl chloride
[Wolfrom and Thompson, J. Am. Chem. Soc., 68 791 (1961)] in 200 ml.
of absolute ether was added slowly to a solution of 4.2 grams of
diazomethane in 500 ml. of absolute ether. The resulting solution
was allowed to stand for about two hours at room temperature and
then concentrated approximately to one-third its volume. The
product was crystallized by the addition of petroleum ether with
cooling and yielded about 10 grams (65% yield) of crude product.
Pure product was obtained by recrystallization from absolute
ethanol, melting point 93.degree.-94.degree. C.
Keto-L-fructose pentacetate
A solution of 10 grams of 1-deoxy-1-diazo-keto-L-fructose
tetracetate and 0.01 gram of cupric acetate in 300 ml. of anhydrous
acetic acid in a 2 liter flask was heated gently and after the
initial violent evolution of gas had subsided, was brought just to
the boiling point. The solvent was removed by distillation under
reduced pressure, the final portion was removed by distillation
with ethanol. The resulting syrup was dissolved in 15 ml. of
ethanol, filtered and allowed to crystallize overnight in a
refrigerator. This yielded 4 grams of crystals, m.p. 65.degree. C.
The syrup obtained from mother liquid was dissolved in 50 ml. of
acetic anhydride containing 0.5 gram of zinc chloride (fresh
fused), allowed to stand overnight at room temperature and heated
90 minutes at 50.degree. C. Excess acetic anhydride was hydrolyzed
by pouring into 200 ml. of ice-water and stirred for 2 hours. The
acetylated sugar was extracted from the water with 200 ml. of
chloroform. The chloroform solution was washed with water, dried
over anhydrous sodium sulfate, filtered and evaporated to a syrup.
This syrup was crystallized from 10 ml. of ethanol and yielded an
additional 3 grams of product.
.beta.-L-fructose hemihydrate
Ten grams of finely powered keto-L-fructose pentacetate was added
to 135 ml. of an aqueous solution of 13 grams of barium hydroxide
octahydrate at 0.degree. C. This mixture was stirred at this
temperature of about 30 minutes at which time all of the
pentacetate was dissolved, and then allowed to stand for an
additional 90 minutes at this temperature. A solution of 3 grams of
oxalic acid in 25 ml. of water was added to precipate most of the
barium ions. The remainder of the barium ions were removed by
stirring the filtered solution with excess of Amberlite IR-100(H+)
cation-exchange resin until the solution no longer gave a positive
test for barium ions with sulfate. The resin was removed by
filtration and the solution was stirred with Duolite A-4(OH.sup.-)
anion-exchange resin until the pH increased to the range of 6.8 to
7. The resin was filtered off and the solution concentrated under
reduced pressure at a temperature below 50.degree. C. The resulting
syrup was crystallized from ethanol at refrigerator temperature to
yield about 4 grams of product. This was recrystallized as
.beta.-L-fructose hemihydrate by dissolving in a small amount of
water, evaporating under reduced pressure and dissolving the syrup
in ethanol; melting point 101.degree.-103.degree. C.
EXAMPLE 4
L-Gulose
2,4-O-Benzylidene-6-deoxy-6-nitro-D-glucitol
A solution of 53.7 grams of syrupy 2,4-O-benzylidene-L-xylose
[Fischer and Piloty, Ber. 24 52 (1891)] in one liter of absolute
methanol and 160 ml. of nitromethane was treated with a solution of
10 grams of metallic sodium in 800 ml. of absolute methanol of 22
hours at room temperature. The reaction mixture was acidified with
a slight excess of glacial acetic acid and concentrated under
reduced pressure. Methanol and nitromethane were removed by the
addition of water and further concentrated under reduced pressure.
The moist crystalline mass was mixed with cold (0.degree. C.)
water, filtered and washed with cold (0.degree. C.) water. This
yielded 34 grams (50% yield) of crude
2,4-O-benzylidene-6-nitro-D-glucitol, m.p. 178.degree.-181.degree.
C.; recrystallization gave a purer product, m.p.
192.degree.-194.degree. C.
6-Deoxy-6-nitro-D-glucitol
Ten grams of 2,4-benzylidene-6-deoxy-6-nitro-D-glucitol was heated
for one hour at 75.degree.-80.degree. C. with 100 ml. of 0.1N
H.sub.2 SO.sub.4. After cooling the solution was extracted three
times with ether to remove the benzaldehyde and neutralized with
excess barium carbonate. The barium carbonate and barium sulfate
were removed by centrifugation and filtration through a precoated
filter. The clear solution was then concentrated under reduced
pressure to a syrup, which crystallized spontaneously after
standing several days. This product was recrystallized from ethyl
acetate containing a little methanol and yielded 5.6 grams (79%
yield) of 6-deoxy-6-nitro-D-glucitol, m.p. 78.degree.-80.degree. C.
On recrystallization from dry ethyl acetate, there were obtained
soft needles, m.p. 81.degree.-83.degree. C., and hard compact
prisms, m.p. 89.degree.-91.degree. C.
L-Glucose Benzylphenylhydrazone
A syrup of 6-deoxy-6-nitro-D-glucitol which was obtained by the
hydrolysis of 13.6 grams of
2,4-benzylidene-6-deoxy-6-nitro-D-glucitol was dissolved in 55 ml.
of 1N sodium hydroxide. This solution was added dropwise to 20 ml.
of vigorously stirred sulfuric acid solution (60% weight/weight).
The acidic solution was then diluted with water and neutralized
with excess barium carbonate, 4 ml. of acetic acid were added and
the barium sulfate was removed by filtration. The clear filtrate
was concentrated under reduced pressure to a syrup which was
dissolved in 100 ml. of 75% ethanol. The ethanolic solution was
filtered and treated with about 10 grams of
1-benzyl-1-phenylhydrazine. This solution was allowed to evaporate
in an open dish with the occasional addition of small amounts of
methanol, until crystallization was complete. The crystals were
freed from the syrup by washing with water and then ether. This
yielded 8.5 grams (67% yield) of crude L-gulose
benzylphenylhydrazone, m.p. 124.degree.-128.degree. C. This was
recrystallized from a solution of 110 ml. of chloroform and 15 ml.
of methanol to give colorless L-gulose benzylphenylhydrazone, m.p.
130.degree.-131.degree. C.
L-Gulose
The L-gulose benzylphenylhydrazone was refluxed for three hours
with 100 ml. of water and 20 ml. of ethanol containing 7.5 ml. of
benzaldehyde and 0.8 grams of benzoic acid. After cooling, the
solution was decanted from the crystals of benzaldehyde
benzylphenylhydrazone and extracted several times with ether to
remove the benzaldehyde and benzoic acid. The solution was then
decolorized with activated carbon and concentrated under reduced
pressure to a colorless syrup to yield 3.4 grams of syrupy
L-gulose.
EXAMPLE 5
.alpha.-L-Galactose
L-Galactono-1,4-lactone
A solution of 21.6 grams (0.1 mole) of sodium D-galacturonate
[Molten, et al, J. Am. Chem. Soc., 61 270 (1939); Pigman, J.
Research Natl. Bur. Standards, 25 301 (1940); Isbell et al, ibid 32
77 (1974)] in 200 ml. of water was placed in a 500 ml. flask and
cooled in an ice bath. With stirring, 100 ml. of cold,
freshly-prepared 0.5M. aqueous solution of sodium borohydride (100%
excess) was added and the reduction mixture allowed to stand
overnight at about 5.degree. C. It was then stirred with 25 ml. of
cation-exchange resin, Amberlite I.R.-120(H+) to decompose
unreacted sodium borohydride, and then poured through a column
containing 250 ml. of resin. The effluent and washings were
concentrated under reduced pressure to a syrup. Methanol was added
to the syrup and this mixture warmed under reduced pressure to
remove the boric acid as methyl borate. This procedure was repeated
two times. The residue was then heated with 25 ml. of Methyl
Cellusolve (2-methoxyethanol) on a boiling water bath for two
hours. Isopropanol was added almost to the point of incipient
turbidity and the solution seeded with crystalline
L-galactone-1,4-lactone. Crystals of L-galactono-1,4-lactone were
separated. Concentration of the mother liquor and addition of
isopropanol gave more crystalline lactone. Recrystallization from
hot ethanol gave about a 90% yield of crystalline
L-galactone-1,4-lactone, m.p. 134.degree. C.
L-Galactose
A mixture of 500 ml. of finely crushed ice, 115 grams of sodium
hydrogen oxalate and 10 grams of L-galactone-1,4-lactone was
agitated in a closely covered, high speed blender with stainless
steel blades. After a few seconds of blending, 260 grams of pellets
of 5% sodium-amalgam was gradually added and agitation was
continued for 15 minutes, during which time the temperature rose to
about 30.degree.-35.degree. C. The resulting solution was decanted
from the mercury and neutralized with dilute sodium hydroxide until
a faint but permanent pink color of phenolphthalein was obtained.
This solution was evaporated under reduced pressure to a volume of
about 100 ml. and treated with five volumes of methanol. The
precipitated salts were separated, washed with a little methanol
and discarded. The filtrate was concentrated under reduced pressure
to about 50 ml. and again treated with five volumes of methanol.
The precipitated salts were again removed by filtration and the
solution after concentration to about 50 ml. was deionized by
passage through a column containing 60 ml. of mixed cation and
anion exchange resins, Amberlite I.R.-120(H+) and Duolite A
4(OH.sup.-). The combined effluent and washings were tested for
ionic impurities by means of a conductivity meter and, when free of
ionic impurities, concentrated under reduced pressure to a thin
syrup. This syrup was dissolved in a minimal amount of methanol and
isopropanol added to the point of incipient turbidity. The crop of
crystals was separated and washed with methanol, and an additional
crop of crystals obtained from the mother liquor by concentration
and addition of methanol to give a total yield of about 80%.
Organoleptic tests were conducted to determine the sweetening power
of the L-hexoses. Exemplary of these is the following conducted
with D-glucose, L-glucose and sucrose (common sugar), wherein
distilled water solutions of both D-glucose and sucrose in
concentrations of 1 mg./ml., 10 mg./ml. and 100 mg./ml. were
prepared. Each of these solutions was divided into three parts and
each tested by a panel of three tasters. Each member of the panel
sampled each of the two solutions at the three different
concentrations, with appropriate rinsing of their mouths after each
taste. The panel had previously been instructed to rate each of the
samples on the basis of 0 to 3, the 0 indicating no sweetness and
the 3 indicating the highest degree of sweetness. The panel was in
agreement that a substantial degree of sweetness, i.e., in the
range of 2-3, was not attained by either the D-glucose or sucrose
until the more concentrated, i.e., 100 mg./ml., solutions were
tasted. This same panel was used to taste test solutions of
L-glucose at a concentration of 100 mg./ml. using the same
procedure. Again, the panel was in agreement that the L-glucose
solution was sweet and a substantial degree of sweetness, i.e., a
2-3 rating, was obtained with the 100 mg./ml. solutions of
L-glucose. Similar results were obtained with the other L-hexose
monosaccharides of this invention. Thus, the minimum concentration
of L-hexose necessary to obtain a substantial degree of sweetness
is about 100 mg./ml.
The above examples are indicative of the methods which may be used
to obtain the L-hexose monosaccharides used in the present
invention. Obviously, other preparation methods may be employed to
obtain the subject L-hexoses used as sweetening agents within the
scope of the present invention. Other 2-aldohexoses which may be
used according to this invention as sweetening agents to prepare
edible food formulations include L-altrose, which may be prepared
from L-arabinose via the intermediate formation of L-ribose and
L-altronic acid [Austin et al., J. Am. Chem. Soc., 56 1153 (1934)],
L-idose, which may be prepared from D-glucose [Meyer et al., Helv.
29 152 (1946)], and L-talose, which may be prepared according to
the procedure of Stallhaar and Reichstein, Helv. 21 3 (1938). Other
L-ketohexoses which may be used as sweetening agents include
L-tagatose, which may be prepared by the alkaline rearrangement of
L-sorbose and L-psicose, which may be prepared by the oxidative
fermentation of allitol by sorbose bacterium [Steiger et al, Helv.
18 790 (1935)].
Other commonly known and employed preparative methods may be used
to prepare the L-hexose monosaccharides of the present invention.
Discussions of such methods may be found in the literature of
carbohydrate chemistry. For example, one general method of
preparing hexoses is based upon the lengthening of the
carbon-to-carbon chain, i.e., preparation of hexoses from the
corresponding pentose. Under this general method are procedures
such as the cyanohydride synthesis (Kiliani-Fischer method),
nitromethane synthesis (Sowden-Fischer method), and diazomethane
synthesis, and each of these are useful in the preparation of the
subject hexoses. Another general method involves a shortening of
the carbon-to-carbon chain, i.e., preparation of hexoses from the
corresponding heptose. Under the general method are procedures such
as the Ruff degradation, the Wohl degradation, the Weeman
degradation, the MacDonald-Fischer degradation and the
Weygand-Lowenfeld degradation and each of these are useful in the
preparation of the subject L-hexoses. Another general method
involves changing the configuration of the corresponding
saccharide. Thus, procedures such as the pyridine and alkaline
rearrangement and glycol synthesis are useful. Discussions of the
methods may be found in W. Pigman, The Carbohydrates, pages 106-132
(Academic Press, New York, 1957), and the references cited
therein.
As has been discussed above, the term L-hexose monosaccharides as
used herein and in the appended claims is used within the standard
meaning in the art. Thus, the prefix "L" refers to the
configuration of the hexose structure according to the Fischer
system of nomenclature as modified by Roranoff. According to this
system, the subject L-hexoses are considered to be those derived
from the fundamental structural glycerose, L-glyceraldehyde of the
formula: ##STR2## by the successive application of the cyanohydrin
synthesis to obtain a hexose. These compounds are configurationally
the direct opposite of those hexoses derived by the same series of
reactions, from the fundamental structural glycerose,
D-glyceraldehyde of the formula: ##STR3##
Similarly, the subject L-ketohexoses are, according to this system,
derived from the fundamental L-ketose, L-erythrulose (L-threulose)
of the formula: ##STR4##
A further discussion of this terminology may be found in W. Pigman,
The Carbohydrates, pages 21-29 (Academic Press, New York, 1957) and
the references cited therein. It is, of course, to be understood
that while the configuration of the L-hexoses, in particular
L-glucose, has been shown structurally in an open chain of Fischer
projection type formula, it is equally within the scope of this
invention that the L-hexoses may have a ring structure, for
example, a pyranose or furanose ring, with the L-configuration, and
still be useful as sweetening agents for edible formulations.
As has been discussed above, the L-hexose monosaccharides are
sweet, soluble in water and stable in aqueous solutions. Therefore,
they are useful for sweetening all types of materials which are
intended for consumption or at least contact with the mouth of the
user, such materials being herein generically designated as edible
materials or foodstuffs. Typical illustrative examples of edible
foodstuffs which may be sweetened according to this invention are
fruits, vegetables, juices or other liquid preparations made from
fruits or vegetables, meat products, particularly those
conventionally treated with sweetened liquors, such as bacon and
ham, milk products such as chocolate dairy drinks, egg products,
such as egg nogs, custards, angel food mixes, salad dressings,
pickles and relishes, ice creams, sherberts and ices, ice milk
products, bakery products, icings, confections and confection
toppings, syrups and flavors, cake and pastry mixes, beverages,
such as carbonated soft drinks, fruit aids, wines, dietary-type
foods, cough syrups and other medicinal preparations such as
pastes, powders, foams and denture-retaining adhesives, mouth
washes and similar oral antiseptic liquids, tobacco products,
adhesives for gumming stamps, envelopes, labels and the like.
In using the sweetening agents of this invention, they are
incorporated in the material to be sweetened in the amount required
to attain the desired level of sweetness. It is obvious that there
is nothing critical about the concentration of sweetening agent
which is used. It is simply a matter of attaining a desired
sweetness level appropriate to the material in question. Moreover,
the technique of sweetening materials with the compounds of the
invention offers no difficulty as the sweetening agent is simply
incorporated with the material to be sweetened. The sweeteners may
be added directly to the material or they may be first incorporated
with a diluent to increase their bulk and added to the material. As
diluent, if needed, one may use liquid or solid carriers, such as
water, glycol, starch, sorbitol, salt, citric acid or other
non-toxic substances compatible with the material to be
sweetened.
While the invention has been described as mainly concerned with
foodstuffs and other non-toxic formulations for human consumption,
it is obviously within the scope of this invention that these
sweetened compositions may be used for consumption by other
animals, such as farm and domestic animals.
While the invention has been described with respect to the use of
L-hexose monosaccharides as the sole sweetening agent, it is to be
understood that they may be used in combination with conventionally
used sweetening agents, e.g., in combination with a minor amount of
sucrose.
* * * * *