MXPA00002557A - SWEETENER SALTS OF N-[N-(3,3-DIMETHYLBUTYL) -L-&agr;-ASPARTYL]-L-PHENYLALANINE 1-METHYL ESTER - Google Patents
SWEETENER SALTS OF N-[N-(3,3-DIMETHYLBUTYL) -L-&agr;-ASPARTYL]-L-PHENYLALANINE 1-METHYL ESTERInfo
- Publication number
- MXPA00002557A MXPA00002557A MXPA/A/2000/002557A MXPA00002557A MXPA00002557A MX PA00002557 A MXPA00002557 A MX PA00002557A MX PA00002557 A MXPA00002557 A MX PA00002557A MX PA00002557 A MXPA00002557 A MX PA00002557A
- Authority
- MX
- Mexico
- Prior art keywords
- phenylalanine
- dimethylbutyl
- sweetener
- methyl ester
- aspartyl
- Prior art date
Links
- IAOZJIPTCAWIRG-QWRGUYRKSA-N Aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 title claims abstract description 43
- 235000003599 food sweetener Nutrition 0.000 title claims abstract description 40
- 239000003765 sweetening agent Substances 0.000 title claims abstract description 40
- 235000010357 aspartame Nutrition 0.000 title abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 239000011780 sodium chloride Substances 0.000 claims abstract description 36
- 239000007788 liquid Substances 0.000 claims abstract description 12
- YGCFIWIQZPHFLU-UHFFFAOYSA-N acesulfame Chemical compound CC1=CC(=O)NS(=O)(=O)O1 YGCFIWIQZPHFLU-UHFFFAOYSA-N 0.000 claims abstract description 11
- CVHZOJJKTDOEJC-UHFFFAOYSA-N Saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229960005164 ACESULFAME Drugs 0.000 claims abstract description 9
- HCAJEUSONLESMK-UHFFFAOYSA-N Cyclamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 claims abstract description 9
- 229940081974 Saccharin Drugs 0.000 claims abstract description 8
- 235000019204 saccharin Nutrition 0.000 claims abstract description 8
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims abstract description 8
- 230000005595 deprotonation Effects 0.000 claims abstract description 7
- 238000010537 deprotonation reaction Methods 0.000 claims abstract description 7
- LPLVUJXQOOQHMX-MYOOOWEVSA-N Glycyrrhizic acid Natural products O=C(O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@H](C(=O)O)O2)[C@@H](O[C@@H]2C(C)(C)[C@H]3[C@@](C)([C@H]4C(=O)C=C5[C@](C)([C@]4(C)CC3)CC[C@]3(C)[C@H]5C[C@](C(=O)O)(C)CC3)CC2)O1 LPLVUJXQOOQHMX-MYOOOWEVSA-N 0.000 claims abstract description 6
- 239000001685 glycyrrhizic acid Substances 0.000 claims abstract description 6
- 229960004949 glycyrrhizic acid Drugs 0.000 claims abstract description 6
- 235000019410 glycyrrhizin Nutrition 0.000 claims abstract description 6
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims abstract description 6
- -1 3,3-dimethylbutyl Chemical group 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 5
- 108010016626 Dipeptides Proteins 0.000 abstract description 3
- 230000002378 acidificating Effects 0.000 abstract description 3
- 150000001447 alkali salts Chemical class 0.000 abstract 1
- 235000013615 non-nutritive sweetener Nutrition 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
- 239000000605 aspartame Substances 0.000 description 12
- 108010011485 Aspartame Proteins 0.000 description 11
- 229960003438 Aspartame Drugs 0.000 description 11
- HLIAVLHNDJUHFG-HOTGVXAUSA-N Neotame Chemical compound CC(C)(C)CCN[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 HLIAVLHNDJUHFG-HOTGVXAUSA-N 0.000 description 10
- 239000004384 Neotame Substances 0.000 description 6
- 235000019412 neotame Nutrition 0.000 description 6
- 108010070257 neotame Proteins 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 5
- 235000013305 food Nutrition 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N D-sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- CZMRCDWAGMRECN-GDQSFJPYSA-N Sucrose Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1)[C@@]1(CO)[C@H](O)[C@@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-GDQSFJPYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 238000005755 formation reaction Methods 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229960005190 Phenylalanine Drugs 0.000 description 2
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Sodium cyclamate Chemical class [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000010410 dusting Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 1
- 229940109275 Cyclamate Drugs 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 229960001462 Sodium Cyclamate Drugs 0.000 description 1
- 229960000716 TONICS Drugs 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 235000012174 carbonated soft drink Nutrition 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003292 diminished Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drugs Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 235000015270 fruit-flavoured drink Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000003389 potentiating Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 235000014438 salad dressings Nutrition 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000001256 tonic Effects 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
Abstract
Dipeptide sweeteners are disclosed that are sweetener salts of N-[N-(3, 3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester represented by formula (I), wherein Xm- is a conjugate base derived by deprotonation of an acidic sweetener, preferably saccharin, acesulfame, cyclamic acid and glycyrrhizic acid;and m=n. Also disclosed is a liquid low-calorie sweetener containing such basic salts.
Description
SALTS SWEETENERS OF ESTHER 1-METYLLIC OF N-fN- (3,3-DIMETHYLBUTYL) -L-a-ASPARTIL1-L-PHENYLALANINE
BACKGROUND OF THE INVENTION 5 FIELD OF THE INVENTION
This invention relates to novel sweeteners. In particular, the invention relates to sweetening salts of the N-alkylated derivative
aspartame, 1-methyl ester of N- [N- (3,3-d.methylbutyl) -L- -aspartyl] -L-phenylalanine, ie neotame. The invention also relates to a low calorie liquid sweetener containing said sweetening salts.
RELATED PREVIOUS TECHNIQUE It is known that several N-substituted derivatives of aspartame, such as those described in U.S. Pat. No. 5,480,668, are useful as sweetening agents. In particular, the N-alkylated derivative of aspartame, 1-methyl ester of N- [N- (3,3-dimethylbutyl) -L-α-aspartyl] -L-20-phenylalanine is known as an extremely strong sweetening agent due to its potency sweetener, which on a weight basis, is reported to be at least 50 times that of aspartame and about 10,000 times that of sucrose.
^ g ^! g ^^ ¡£ * ^ iai¡M iuj | MßHÍ | a | H || t ^ mn Because sweetening agents are often used in aqueous solutions and beverages, it is important that they have a dissolving rate acceptable and an effective level of solubility to be feasible from the commercial point of view. U.S. Patent No. 5, 4,031, 258 discloses certain inorganic salts of dipeptide sweeteners that provide improved dissolution and solubility. European Patent Application No. EP 768,041 and Spanish Patent 85-547855 describe salts formed between aspartame and acid sweetening compounds, such as saccharin, cyclamic acid and acesulfame. It is said that these sweetener salts
have an improved flavor similar to sucrose. The N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester salts, however, are not described or suggested in any reference. It is known that the physical properties, as well as the stability of aspartame and other peptides can be modified by means of the
conversion of its salts. This is described, for example, in U.S. Patent Nos. 4,031, 258 and 4,153,737. U.S. Patent 4,173,737 also discloses low-calorie concentrated liquid sweeteners. Structurally, however, 1-methyl ester of N- [N- (3,3-20-dimethylbutyl) -La-aspartyl] -L-phenylalanine and aspartame differ in that 1-methyl ester of N- [N - (3,3-dimethylbutyl) -La-aspartyl] -L-phenylalanine, a substituent of volumetric neohexyl is present in the nitrogen of the amine.
_ ^ - tfiÍ? ta-a ^ í * -h-¡-i-i
Aspartame Neotame This structural difference results in serious differences in the physical and chemical properties of these compounds. For example, the melting point of N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester is 80 ° C, whereas for aspartame it is 248 ° C. In addition, N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester has a much higher solubility in organic solvents than aspartame, and a much lower solubility in water. It is also known that N- [N- (3,3-dimethylbutyl) -L-α-aspartyl] -L-phenylalanine 1-methyl ester has greater stability than aspartame under some pH conditions, as described in the US Pat. United States No. 5,480,688. The difference expressed in sweetness between the two compounds is additional evidence of their chemical inequality. Moreover, it is also known that a primary amino group such as that of aspartame (pKa 7.7) generally has a pKa different from those of the secondary amino group such as that of 1-methyl ester of N- [N- (3,3- dimethylbutyl) -La-aspartyl] -L-phenylalanine (pKa 8.1). In addition, it is known that the pKa of an amino acid has a profound impact on food applications (Labuza, T.P. and Basisier, M.W., 1992, "Physical Chemistry of Foods", H.G.
Schwartzber and R.W. Hartel (Eds.), Marcel Dekker, Inc., New York). It is also well known that a secondary amine can not form compounds of the Schiff base type with carbonyl compounds while a primary amine can. In addition, N- [N- (3,3-dimethylbutyl) -L-a-5-aspartyl] -L-phenylalanine-1-methyl ester exhibits a physiologically different behavior than aspartame as exemplified by the dramatic difference in sweetness. These differences are clear indications that the characteristics and properties of one can not suggest those of the other. Although N- [N- (3,3-dimethylbutyl) -L-aspartyl] -10 L-phenylalanine is a highly potent sweetener, it is poorly soluble in water and can cause dusting problems . It would also be convenient to modify and improve the flavor properties of N- [N- (3,3-dimethyl-butyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester to suit a specific application. Therefore, there is a need for ester derivatives
1-N- [N- (3,3-dimethylbutyl) -L- -aspartyl] -L-phenylalanine methyl ester having improved taste, good dissolution properties and solubility in aqueous systems and avoiding problems of dust formation with Frequently found in fine powders. By forming salts with acidic sweeteners, such properties can be achieved.
BRIEF DESCRIPTION OF THE INVENTION
This invention relates to dipeptide sweeteners which are sweetening salts of N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester which have good dissolution properties and solubility in aqueous systems. In particular, the N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester salts of this invention are represented by the formula
Wherein Xm "is selected from the group consisting of conjugated bases derived from deprotonation of acid sweeteners, preferably saccharin, acesulfame, cyclamic acid or glycyrrhizic acid, and m = n, preferably n is 1, 2 or 3. The invention also refers to a low calorie liquid sweetener containing the salts of this invention.
BRIEF DESCRIPTION OF THE DRAWING
The figure is a graph comparing the aqueous solution of 1-methyl ester N- [N- (3,3-dimethylbutyl) -La-aspartl] -L-phenylalanine in an objective concentration of 0.05% by weight with equivalent concentrations of neotame, that is, the concentration of the neotame presented in each case is the same, of the acesulfame and of the salts of cyclamate of 1-methyl ester of N- [N- (3,3-dimethylbutyl) -La-aspartyl] - L-phenylalanine.
DETAILED DESCRIPTION OF THE INVENTION
This invention is directed to sweetening salts of N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester, ie, sweetener salts of neotame. U.S. Patent No. 5,480,668, U.S. Patent No. 5,510,508 and U.S. Patent No. 5,728,862, which describe the preparation of N- [N- (3,3-dimethylbutyl) -l-1-methyl ester -aspartyl] -L-phenylalanine are incorporated by reference herein as if they were fully disclosed. Thus, the starting material can easily be prepared by a person skilled in the art without the need for experimentation. The sweetening salts of this invention can be prepared by adding N- [N- (3,3-dimethylbutyl) -L-α-aspartyl] -L-phenylalanine 1-methyl ester and an acid sweetening compound to an amount of a solvent effective to dissolve both the N- [N- (3,3-dimethylbutyl) -L- -aspartyl] -L-phenylalanine 1-methyl ester and the acid compound, and then stirring for a time to achieve salt formation. Suitable solvents include ethane, methanol, acetone, acetonitrile, ethyl acetate, water and t-buylmethyl ether. The product of the salt can be recovered by evaporating the solvent in vacuo. The product of the salt can also be recovered by drying by freezing or by spray drying the resulting solution. These salts can also be prepared by adding acid (such as hydrochloric acid, sulfuric acid or phosphoric acid) to a suspension of N- [N- (3,3-dimethylbutyl) -La-aspartyl] -L-phenylalanine 1-methyl ester. and acid salt sweetener (such as sodium saccharin, acesulfame-K potassium salt or sodium cyclamate) in a solvent such as water or alcohol. The sweetening salts of N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester prepared under these conditions show no racemisation. The acidic sweetening compounds used in the preparation of the salts of this invention are basically selected from sweetening compounds having a pKa effectively lower than the pKa of the functionality of the N-1-methyl ester of N- [N- (3,3- dimethylbutyl) -L-oc-aspartyl] -L-phenylalanine to result in the formation of the desired salt. Such compounds include, for example, saccharin, acesulfame, cyclohexyl sulfamic acid (hereinafter cyclamic acid) and glycyrrhizic acid. As such, Xm "is the conjugate anion base derived from deprotonation of the acid compound.
In particular, the preferred sweetener salts of this invention include the salts formed between N- [N- (3,3-dimethylbutyl) -L-α-aspartyl] -L-phenylalanine 1-methyl ester and a Acid sweetener chosen from the group consisting of saccharin, acesulfame, cyclamic acid and glycyrrhizic acid. It is believed that the salts of this invention provide a number of improved properties over those of N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester. In particular, the aqueous solubility is increased and the rate of dissolution of the composition is greatly improved. These sweetener salts of neotame are sweet tasting. It is also believed that these salts will have an improved flavor. Thus, N- [N- (3,3-dimethylbutyl) -L-α-aspartyl] -L-phenylalanine 1-methyl ester salts will be particularly useful in beverage systems, especially since the additional methods or mechanical preparations are diminished or they are not necessary to favor a rapid dissolution as desired in a tabletop sweetener. The salts of this invention can be mixed with known body-forming agents to prepare tablets, powdered sweeteners and granulates using methods well known to those skilled in the art. Another advantage of the salts of this invention is that they do not present the dusting problems associated with N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester. The salts can also be used to prepare a low calorie liquid sweetener by dissolving a high concentration of the sweetening salt of this invention in an aqueous system or
alcohol, for example, water, propylene glycol, a water / propylene glycol mixture, ethanol or a water / ethanol mixture. Said low calorie liquid sweetener may find use in food products such as gelatin desserts, fruit flavored drinks, cereal, cake flour, fruit juices, syrups, salad dressings, pet foods, carbonated soft drinks, sweeteners of table and similar. Such utilities are not restrictive since other applications may include cough medicines, tonics and the like. One embodiment of this invention of particular interest contemplates a liquid tabletop sweetener in replacement of sucrose and other known sweeteners. The low-calorie liquid sweetener will generally contain up to about 40% by weight of the N- [N- (3,3-dimethylbutyl) -La-aspartl] -L-phenylalanine 1-methyl ester salt, depending on the concentration , of course, of the desired end use. It is intended that the examples below be an illustration of certain preferred embodiments of the invention, and no limitation of the invention is implied.
; -t? EXAMPLE 1 Acesulfame salt of N- [N- (3,3-dimethylbutyl) -L-a-aspartip-L-phenylalanine 1-methyl ester)
Acesulfame (6.30 g, 0.0386 moles) and 1-methyl ester of N- [N- (3,3-dimethylbutyl) -La-aspartyl] -L-phenylalanine (15.31 g, 0.0386 moles) were dissolved in methanol (100 ml ) at room temperature to form a clear solution. Most of the methanol was removed using a rotary evaporator at 33 ° C under vacuum. The residual solvent was removed
using a mechanical pump. The yield of the title compound was 20.97 g. Acesulfame salt of N- [N- (3,3-dimethylbutyl) -L- a-aspartyl] -L-phenylalanine 1-methyl ester (0.2 g) was dissolved in water (100 ml) in less than 120 seconds (visual observation). Water content (Karl Fisher): 1.81%. 15 Analysis calculated for C24H35N3? 9S. 0.55H2O: C, 52.27; H,
6. 60; N, 7.62; S, 5.81. Found: C, 52.55; H, 6.50; N, 7.64; S, 5.91. 1 H NMR (DMSO-d 6): d 0.81 (S, 9 H, t-butyl), 1.42 (m, 2 H, -CH 2 -), 1.89 (s, 3 H, CH 3 -C = C), 2.6-3.1 (m, 6H, -CH2-), 3.62 (s, 3H, CH3-O), 4.06 (m, 1 H, -CH-), 4.59 (m, 1 H, -CH-), 5.27 (s, 1 H, HC = C), 7.2-7.3 (m, 5H, phenyl).
EXAMPLE 2 Salt of 1-methyl ester of N-fN- (3,3-dimethylbutyl) -L-a-aspartn-L-phenylalanine
Saccharin (7.62 g, 0.0416 moles) and N- [N- (3,3-dimethylbutyl) -L-aspartyl] -L-phenylalanine 1-methyl ester (16.42 g, 0.416 moles) were dissolved in methanol (100 ml) at room temperature to form a clear solution. Most of the methanol was removed using a rotary evaporator at 33 ° C under vacuum. The residual solvent was removed using a mechanical pump. The yield of the title compound was 23.30 g. The saccharin salt of neo-a-aspartame (0.2 g) was dissolved in water (100 ml) in less than 120 seconds (visual observation). Water content (Karl Fisher): 1.16%. Analysis calculated for C27H35N3? 8S. 0.37H2O: C, 57.06; H, 6.34; N, 7.39; S, 5.64. Found: C, 57.23; H, 6.30; N, 7.42; S, 5.69. 1 H NMR (DMSO-d 6): d 0.80 (S, 9 H, t-butyl), 1.42 (m, 2 H, -CH 2 -), 2.5-3.1 (m, 6 H, CH 2 -), 3.62 (s, 3 H, CH 3 -O), 4.05 (m, 1 H, -CH-), 4.58 (m, 1 H, -CH), 7.1-7.7 (m, 9H, phenyl).
EXAMPLE 3 N-fN- (3,3-dimethylbutyl) -L- - aspartyl-L-phenylalanine 1-methyl ester cyclamic acid salt
Cyclamic acid (7.33 g, 0.0409 mol) and 1-methyl ester of N- [N- (3,3-dimethylbutyl) -La-aspartyl] -L-phenylalanine (16.22 g, 0.409 mol) were dissolved in methanol (100 ml ) at room temperature to form a clear solution. Most of the methanol was removed using a rotary evaporator at 33 ° C under vacuum. The residual solvent was removed using a mechanical pump. The yield of the title compound was 22.75 g. The cyclic salt of N- [N- (3,3-dimethylbutyl) -L-aspartyl] -L-phenylalanine 1-methyl ester (0.2 g) was dissolved in water (100 ml) in less than 120 seconds (visual observation ). Water content (Karl Fisher): 0.94%. Analysis Calculated for C 26 H 43 N 3 O 8 S.0.29H 2 O: C, 55.47; H,
7. 80; N, 7.46; S, 5.70. Found: C, 55.68; H, 7.72; N, 7.48; S, 5.69. 1 H NMR (DMSO-de): d 0.80 (s, 9H, t-butyl), 1.0-2.0 (m, 12H, -CH2-), 2.5-3.1 (m, 7H, -CH2- and -CH-), 3.62 (s, 3H, CH3-O), 3.90 (m, 1 H, -CH-), 4.57 (m, 1 H, -CH-), 7.1-7.3 (m, 5H, phenyl).
COMPARATIVE EXAMPLE 1 N-rN- (3,3-dimethylbutyl) -L-o: -aspartiH-L-phenylalanine 1-methyl ester solution in water
N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine ester (1 - 0.2 g) was dissolved in water (100 ml). The compound completely dissolved in 5-8 minutes (visual observation). The solution of 1.0 g of N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester in 100 ml of water required approximately 45 minutes. Other variations and modifications of this invention will be obvious to those skilled in the art. This invention is not limited except as set forth in the following claims.
. t -. ^ t - ^^ - M.i -.- ^^? m ^^ M * * ^ ^ ***. ^ .. ^ ¿et ^ j? átS.
Claims (6)
1. - A 1-methyl ester salt of N- [N- (3,3-dimethylbutyl) -L- -aspartyl] -L-phenylalanine represented by the formula wherein Xm "is a conjugate base derived from deprotonation of an acid sweetener and m = n 2.- A salt according to claim 1, further characterized in that n is 1, 2 or 3. 3.- A salt in accordance with claim 1, further characterized in that n is 1 and Xm "is a conjugate base derived from deprotonation of an acid sweetener selected from the group consisting of saccharin, acesulfame, cyclamic acid and glycyrrhizic acid. 4. A low calorie liquid sweetener composition comprising a salt of a dipeptide sweetener represented by the formula ^ jj f | ^ ¡| ^^ jgig i gH ' wherein Xm "is a conjugate base derived from deprotonation of an acid sweetener, and m = n, dissolved in a solvent or consumer solvents in a concentration of up to about 40% by weight of the composition to provide a low calorie liquid sweetener of High concentration 5. A low calorie liquid sweetener according to claim 4, further characterized in that the solvent is ethanol 6. A low calorie liquid sweetener according to claim 5, further characterized in that n is 1 and Xm "is a conjugate base derived from deprotonation of an acid sweetener selected from the group consisting of saccharin, acesulfame, cyclamic acid and glycyrrhizic acid. JA ^^ 'a ^^ - -. ^ aütA ^
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US60/058,507 | 1997-09-11 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA00002557A true MXPA00002557A (en) | 2001-11-21 |
Family
ID=
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6129942A (en) | Sweetener salts of N-[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester | |
US20040105928A1 (en) | Sweetener compositions and uses thereof | |
CZ331994A3 (en) | Novel compounds usable as sweeteners and process for preparing thereof | |
AU751006B2 (en) | Basic salts of N-(N-(3,3-dimethylbutyl)-L-alpha-aspartyl)-L-phenylalanine 1-methyl ester | |
NZ247923A (en) | Artificial sweetener comprising an l-aspartyl-d-alpha-aminoalkanoyl-(s)-alpha-alkylbenzyl amide; sweetening edible compositions | |
US6146680A (en) | Metal complexes of N-[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester | |
US6180156B1 (en) | Acid salts of N-[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester | |
US3972860A (en) | L-aspartyl-L-phenylglycine esters of lower alkanols | |
MXPA00002557A (en) | SWEETENER SALTS OF N-[N-(3,3-DIMETHYLBUTYL) -L-&agr;-ASPARTYL]-L-PHENYLALANINE 1-METHYL ESTER | |
JPS61200999A (en) | Aspartylalanine 2-pinanyl or fenchyl ester | |
CZ2000815A3 (en) | Acid salts of 1-methyl ester of N-[N-(3,3-dimethylbutyl)-L-alpha-aspartyl]-L-phenylalanine | |
MXPA00002539A (en) | BASIC SALTS OF N-[N-(3,3-DIMETHYLBUTYL)-L-&agr;-ASPARTYL]-L-PHENYLALANINE 1-METHYL ESTER | |
MXPA00002552A (en) | METAL COMPLEXES OF N-[N-(3,3-DIMETHYLBUTYL) -L-&agr;-ASPARTYL]-L-PHENYLALANINE 1-METHYL ESTER | |
CZ2000819A3 (en) | Salts of 1-methyl ester of N-[N-(3,3-dimethylbutyl)-L-alpha-aspartyl]-L-phenylalanine sweetening agent | |
MXPA00002540A (en) | ACID SALTS OF N-[N-(3,3-DIMETHYLBUTYL)-L-&agr;-ASPARTYL]-L-PHENYLALANINE 1-METHYL ESTER | |
EP0109685A1 (en) | Enhanced-solubility aspartame compounds | |
CZ2000818A3 (en) | Complexes of 1-methyl ester of N-[N-(3,3-dimethylbutyl)-L-alpha-aspartyl]-L-phenylalanine with metals | |
CZ2000814A3 (en) | Basic salts of 1-methyl ester of N-[N-(3,3-dimethylbutyl)-L-alpha-aspartyl]-L-phenylalanine |