EP0805799A1 - NOVEL SWEETENERS DERIVED FROM 3,4-DISUBSTITUTED $g(a)-BENZENEAMIDE N-(4-CYANOPHENYLCARBAMOYL OR 2-CYANOPYRID-5-YLCARBAMOYL)-L-ASPARTIC OR L-GLUTAMIC ACIDS - Google Patents

NOVEL SWEETENERS DERIVED FROM 3,4-DISUBSTITUTED $g(a)-BENZENEAMIDE N-(4-CYANOPHENYLCARBAMOYL OR 2-CYANOPYRID-5-YLCARBAMOYL)-L-ASPARTIC OR L-GLUTAMIC ACIDS

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Publication number
EP0805799A1
EP0805799A1 EP96901851A EP96901851A EP0805799A1 EP 0805799 A1 EP0805799 A1 EP 0805799A1 EP 96901851 A EP96901851 A EP 96901851A EP 96901851 A EP96901851 A EP 96901851A EP 0805799 A1 EP0805799 A1 EP 0805799A1
Authority
EP
European Patent Office
Prior art keywords
aspartic
cyanophenylcarbamoyl
acid
sweetening
cyanopyrid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP96901851A
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German (de)
French (fr)
Inventor
Claude Nofre
Jean-Marie Tinti
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Universite Claude Bernard Lyon 1 UCBL
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Universite Claude Bernard Lyon 1 UCBL
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Publication of EP0805799A1 publication Critical patent/EP0805799A1/en
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/84—Nitriles
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/30—Artificial sweetening agents
    • A23L27/31—Artificial sweetening agents containing amino acids, nucleotides, peptides or derivatives
    • A23L27/32—Artificial sweetening agents containing amino acids, nucleotides, peptides or derivatives containing dipeptides or derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • New sweetening agents derived from N- (4-cyanophenylcarbamoyl 2-cyanopyrid-5-ylcarbamoyl) -L-asnartic or L-glutamic ⁇ -3,4-disubstituted amino acids.
  • the present invention relates to new sweetening agents derived from N- (4-cyanophenylcarbamoyl or 2-cyanopyrid-5-ylcarbamoyl) -L-aspartic or L-glutamic ⁇ -benzene acids.
  • These new sweetening agents of very high sweetening intensity are particularly useful for sweetening various products, and in particular carbonated drinks, food, confectionery, pastries, chewing gum, hygiene products, cosmetics, articles toiletries, pharmaceutical and veterinary products and their equivalents.
  • a sweetening agent to be usable on an industrial scale, must in particular have an intense sweetening power, making it possible to limit its cost of use.
  • the new compounds according to the present invention exhibit extremely high sweetening activities since they are, on a weight basis, up to 50,000 times more powerful than sucrose (table sugar).
  • the most used is a dipeptide derivative, NL- ⁇ -aspartyl-L-phenylalanine 1-methyl ester, better known under the name of aspartame (US 3,492,131).
  • the main advantages of this compound are its excellent organoleptic properties and its chemical constitution based on two natural amino acids, L-aspartic acid and L-phenylalanine.
  • the extremely high sweetening intensity of the compounds of the invention has the advantage of making them low cost sweeteners.
  • the preferred sweeteners of the present invention are in fact, on a weight basis, up to 50,000 times sweeter than sugar, which amounts to saying that 1 gram of the preferred compounds of the invention is sufficient to replace up to 50 kilograms of sugar. Since the preferred sweeteners of the present invention are approximately 250 to 400 times more powerful than aspartame itself, their cost of use will therefore be very low compared to aspartame, which makes it advantageous to envisage their industrial application.
  • R 1 and R 3 are hydrogen or halogen atoms, or groups CN, NO 2 , R '(R' being an alkyl group of 1 to 6 carbon atoms), COOR “, R” CO, halomethyl , R “O, CONHR”, SO 2 R “or SOR” (R “being an alkyl group of 1 to 4 carbon atoms);
  • R 2 is an oxygen or sulfur atom
  • n 0, 1 or 2; and the configuration of the carbon atom indicated C *, carrying an amino group, being L or DL.
  • Y is a CH group or a nitrogen atom
  • A is an oxygen atom
  • n 1 or 2
  • R is a 3,4-disubstituted phenyl radical chosen from the groups:
  • a particularly advantageous embodiment of the invention is N- (4-cyanophenylcarbamoyl) -L-aspartic- ⁇ -3,4-di thylbenzenamide acid of formula:
  • Another particularly advantageous embodiment of the invention is N- (2-cyanopyrid-5- acid ylcarbamoyl) -L-aspartic- ⁇ -3,4-dimethylbenzenamide of formula:
  • N- (4-cyanophenylcarbamoyl) -L-aspartic- ⁇ -3,4-methylenedioxy benzenide N- acid (2-cyanopyrid-5-ylcarbamoyl) -L-aspartic- ⁇ -3,4-methylenedioxybenzenamide
  • N- (4-cyanophenylcarbamoyl) -L-aspartic- ⁇ -3-hydroxy-4-methoxybenzenamide N- (2-cyanopyrid-5-ylcarbamoyl) -L-aspartic- ⁇ -3-hydroxy-4-methoxybenzenamide
  • the compounds of the invention are therefore distinguished from the compounds described in document JP 86-260052 by the very specific nature and the position of the substituents attached to the benzene group. Indeed, in this prior document, the benzene cycle of the benzene group of the compounds described and claimed is monosubstituted, and, for the examples mentioned, only in position 4 (para).
  • the phenyl group R is simultaneously substituted in positions 3 (meta) and 4 (para) by specific groups.
  • the choice in the compounds of the invention of this new group R results in a spectacular increase in the sweetening power, which can reach 10 (ten) times that of the compounds of the prior art, and consequently a significant reduction in the cost of use of such compounds.
  • the sweetening agents of the present invention can be added to any edible product in which it is desired to provide a sweet taste, provided that they are added in sufficient proportions to reach the desired level of sweetness.
  • the optimal concentration of use of the sweetening agent will depend on various factors such as, for example, the sweetness of the sweetening agent, the conditions of storage and use of the products, the particular constituents of the products and the level of desired sweetness. Any qualified person can easily determine the optimal proportion of sweetening agent to be used to obtain an edible product by performing routine sensory analyzes.
  • the sweetening agents of the present invention will, in general, be added to the edible products in proportions ranging, depending on the sweetening power of the compound, from 0.5 mg to 50 mg of sweetening agent per kilogram or per liter of edible product.
  • the concentrated products will obviously contain higher amounts of sweetening agent, and will then be diluted according to the final intentions of use.
  • the sweetening agents of the present invention can be added in pure form to the products to be sweetened, but, because of their high sweetening power, they are generally mixed with a carrier ("carrier”) or with a bulking agent (“bulking agent”). ”) appropriate.
  • the appropriate carriers or bulking agents are chosen from the group consisting of polydextrose, starch, maltodextrins, cellulose, methylcellulose, carboxymethylcellulose and other derivatives of cellulose, sodium alginate, pectins, gums, lactose, maltose, glucose, leucine, glycerol, mannitol, sorbitol, sodium bicarbonate, phosphoric, citric, tartaric, fumaric, benzoic, sorbic, propionic acids, and their sodium salts , potassium and calcium, and their equivalents.
  • the sweetening agents in accordance with the invention may, in an edible product, be used alone, as the sole sweetening agent, or in combination with other sweetening agents such as sucrose, corn syrup, fructose, derivatives or the like sweetened dipeptides (aspartame, alitame), neohesperidin dihydrochalcone, hydrogenated isomaltulose, stevioside, sugars L, glycyrrhizin, xylitol, sorbitol, mannitol, acesulfame, saccharin and its sodium salts, potassium, ammonium and calcium, cyclamic acid and its sodium, potassium and calcium salts, sucralose, monellin, thaumatin, and their equivalents.
  • sweetening agents such as sucrose, corn syrup, fructose, derivatives or the like sweetened dipeptides (aspartame, alitame), neohesperidin dihydrochalcone
  • the compounds of the invention can also be used either in their acid form or in their salt form obtained using physiologically acceptable inorganic or organic bases, which has the effect of increasing their solubility.
  • these compounds are salified in the form of sodium, potassium, ammonium, calcium or magnesium salts.
  • the preparation of the compounds of the invention uses in particular the methods commonly used for peptide synthesis (see for example M. Bodansky and A. Bodansky, The Practice of Peptide Synthesis, Springer Verlag, Berlin, 1984).
  • the purification of the compounds of the invention is carried out according to standard techniques such as recrystallization or chromatography. Their structure and purity have been controlled by conventional techniques (thin layer chromatography, high performance liquid chromatography, infrared spectrometry, nuclear magnetic resonance, elementary analysis).
  • the sweetening power of the compounds described in the examples was evaluated by a group of eight experienced people. For this, the compounds, in aqueous solution at variable concentrations, are compared, in terms of taste, to a 2% sucrose control solution. The sweetening power of the compound, tested relative to sucrose, then corresponds to the weight ratio which exists between the compound and sucrose at equal sweetening intensity, that is to say when the sweet flavors of the solution of the tested compound and of the sucrose control solution is considered, by a majority of people, to have the same sweetening intensity.
  • N- (4-cyanophenylcarbamoyl) -L-aspartic- ⁇ - 3,4-dimethylbenzenamide has a sweetening power which is, on a weight basis, 50,000 times higher than that of sucrose compared to a sucrose solution at 2%.
  • the sweetening power of other compounds according to the invention obtained according to an experimental protocol similar to that described above and which those skilled in the art will easily find, is given in Table 1.

Abstract

Novel high-potency sweeteners of formula (I), wherein Y is a CH group or a nitrogen atom, A is an oxygen atom, n is 1 or 2, and R is a 3,4-disubstituted phenyl group, and physiologically acceptable salts thereof. Such compounds are useful as sweeteners.

Description

Nouveaux agents édulcorants dérivant des acides N-(4- cyanophénylcarbamoyl 2-cyanopyrid-5-ylcarbamoyl)-L-asnartique ou L-glutamique α-benzènamides 3,4-disubstitués. New sweetening agents derived from N- (4-cyanophenylcarbamoyl 2-cyanopyrid-5-ylcarbamoyl) -L-asnartic or L-glutamic α-3,4-disubstituted amino acids.
La présente invention a pour objet de nouveaux agents édulcorants dérivant des acides N- (4-cyanophénylcarbamoyl ou 2-cyanopyrid-5-ylcarbamoyl)-L-aspartique ou L-glutamique α-benzènamides. Ces nouveaux agents édulcorants de très haute intensité édulcorante sont particulièrement utiles pour édulcorer des produits variés, et en particulier les boissons gazeuses, les aliments, les confiseries, les pâtisseries, les chewing- gums, les produits d'hygiène, les cosmétiques, les articles de toilette, les produits pharmaceutiques et vétérinaires et leurs équivalents. The present invention relates to new sweetening agents derived from N- (4-cyanophenylcarbamoyl or 2-cyanopyrid-5-ylcarbamoyl) -L-aspartic or L-glutamic α-benzene acids. These new sweetening agents of very high sweetening intensity are particularly useful for sweetening various products, and in particular carbonated drinks, food, confectionery, pastries, chewing gum, hygiene products, cosmetics, articles toiletries, pharmaceutical and veterinary products and their equivalents.
On sait qu'un agent édulcorant, pour être utilisable à l'échelle industrielle, doit notamment posséder un pouvoir sucrant intense, permettant de limiter son coût d'utilisation.  It is known that a sweetening agent, to be usable on an industrial scale, must in particular have an intense sweetening power, making it possible to limit its cost of use.
Les nouveaux composés conformes à la présente invention présentent des activités édulcorantes extrêmement élevées puisqu'ils sont, sur une base pondérale, jusqu'à 50 000 fois plus puissants que le saccharose (sucre de table). Parmi les agents édulcorants artificiels actuellement commercialisés, le plus utilisé est un dérivé dipeptidique, le N-L-α-aspartyl-L-phénylalanine 1-méthyl ester, plus connu sous le nom d'aspartame (US 3,492,131). Les principaux avantages de ce composé sont ses excellentes propriétés organoleptiques et sa constitution chimique à base de deux amino acides naturels, l'acide L-aspartique et la L- phénylalanine. En revanche, son pouvoir édulcorant est relativement faible puisqu'il n'est, sur une base pondérale, que seulement 120 à 180 fois plus élevé que celui du saccharose, ce qui signifie qu'il faut fournir 1 gramme d'aspartame pour remplacer 120 à 180 grammes de sucre. Le pouvoir édulcorant relativement faible de l'aspartame, associé à son coût de fabrication assez élevé du fait de sa structure dipeptidique, en fait donc un édulcorant cher, ce qui constitue son principal inconvénient dans le cadre de son utilisation industrielle. The new compounds according to the present invention exhibit extremely high sweetening activities since they are, on a weight basis, up to 50,000 times more powerful than sucrose (table sugar). Among the artificial sweetening agents currently on the market, the most used is a dipeptide derivative, NL-α-aspartyl-L-phenylalanine 1-methyl ester, better known under the name of aspartame (US 3,492,131). The main advantages of this compound are its excellent organoleptic properties and its chemical constitution based on two natural amino acids, L-aspartic acid and L-phenylalanine. On the other hand, its sweetening power is relatively weak since it is, on a weight basis, only 120 to 180 times higher than that of sucrose, which means that you have to provide 1 gram of aspartame to replace 120 180 grams of sugar. The relatively weak sweetening power of aspartame, associated with its fairly high manufacturing cost due to its dipeptide structure, therefore makes it an expensive sweetener, which constitutes its main drawback in the context of its industrial use.
L'intensité édulcorante extrêmement élevée des composés de l'invention, associée à leur facilité de préparation, a pour avantage d'en faire des édulcorants de faible prix de revient. Les édulcorants préférés de la présente invention sont en effet, sur une base pondérale, jusqu'à 50 000 fois plus sucrés que le sucre, ce qui revient à dire que 1 gramme des composés préférés de l'invention suffit à remplacer jusqu'à 50 kilogrammes de sucre. Les édulcorants préférés de la présente invention étant environ 250 à 400 fois plus puissants que l'aspartame lui-même, leur coût d'utilisation sera donc très bas par rapport à l'aspartame, ce qui laisse favorablement envisager leur application industrielle.  The extremely high sweetening intensity of the compounds of the invention, associated with their ease of preparation, has the advantage of making them low cost sweeteners. The preferred sweeteners of the present invention are in fact, on a weight basis, up to 50,000 times sweeter than sugar, which amounts to saying that 1 gram of the preferred compounds of the invention is sufficient to replace up to 50 kilograms of sugar. Since the preferred sweeteners of the present invention are approximately 250 to 400 times more powerful than aspartame itself, their cost of use will therefore be very low compared to aspartame, which makes it advantageous to envisage their industrial application.
Dans le document JP 86-260052, Tsuchiya et al . ont décrit des composés édulcorants répondant à la formule générale suivante :  In JP 86-260052, Tsuchiya et al. have described sweetening compounds corresponding to the following general formula:
dans laquelle : in which :
R1 et R3 sont des atomes d'hydrogène ou d'halogène, ou des groupes CN, NO2, R' (R' étant un groupe alkyle de 1 à 6 atomes de carbone), COOR" , R"CO, halogénométhyle, R"O, CONHR", SO2R" ou SOR" (R" étant un groupe alkyle de 1 à 4 atomes de carbone); R 1 and R 3 are hydrogen or halogen atoms, or groups CN, NO 2 , R '(R' being an alkyl group of 1 to 6 carbon atoms), COOR ", R" CO, halomethyl , R "O, CONHR", SO 2 R "or SOR" (R "being an alkyl group of 1 to 4 carbon atoms);
R2 est un atome d'oxygène ou de soufre; R 2 is an oxygen or sulfur atom;
n est 0, 1 ou 2; et la configuration de l'atome de carbone indiqué C*, porteur d'un groupe amino, étant L ou DL. n is 0, 1 or 2; and the configuration of the carbon atom indicated C *, carrying an amino group, being L or DL.
Dans ce document, on ne trouve d'indication chiffrée relative au pouvoir sucrant que pour seulement 2 (deux) composés revendiqués, à savoir, l'acide N-(4-nitrophénylcarbamoyl)-L-aspartique-α-4-chlorobenzènamide de formule :  In this document, there are only quantitative indications relating to the sweetening power for only 2 (two) claimed compounds, namely, N- (4-nitrophenylcarbamoyl) -L-aspartic-α-4-chlorobenzenamide of formula :
qui est décrit comme ayant un pouvoir sucrant de 5 400 fois celui du saccharose, et l'acide N- (4-nitrophénylcarbamoyl)-L-aspartique-α-4-cyanobenzènamide de formule : which is described as having a sweetening power of 5,400 times that of sucrose, and N- (4-nitrophenylcarbamoyl) -L-aspartic-α-4-cyanobenzenamide of formula:
qui est décrit comme ayant un pouvoir sucrant de 4 800 fois celui du saccharose. which is described as having a sweetening power of 4,800 times that of sucrose.
II a été découvert, et ceci constitue le fondement de l'invention, que le pouvoir sucrant de certains autres dérivés des acides N-(4-cyanophénylcarbamoyl ou 2-cyanopyrid-5-ylcarbamoyl)-L-aspartique ou L-glutamique α-benzènamides était puissamment augmenté, de manière tout à fait imprévisible, lorsque le groupe benzènamide est simultanément substitué sur les positions 3 (meta) et 4 (p a ra ) par des substituants convenablement sélectionnés. Or, on sait qu'une modification, même mineure, de la structure d'un édulcorant peut entraîner une perte totale de son activité. Il est donc tout à fait inattendu qu'une double substitution sur le groupe benzènamide puisse, non pas supprimer l'activité édulcorante, mais au contraire l'augmenter fortement par rapport à l'activité des composés monosubstitués décrits dans l'art antérieur. It has been discovered, and this constitutes the basis of the invention, that the sweetening power of certain other derivatives of N- (4-cyanophenylcarbamoyl or 2-cyanopyrid-5-ylcarbamoyl) -L-aspartic or L-glutamic acid α- Benzenamides was strongly increased, in a completely unpredictable manner, when the benzene group is simultaneously substituted in the 3 (meta) and 4 (pa ra) positions by suitably selected substituents. Now, we know that even a modification minor, the structure of a sweetener can lead to a total loss of its activity. It is therefore completely unexpected that a double substitution on the benzene group may not suppress the sweetening activity, but on the contrary greatly increase it compared to the activity of the monosubstituted compounds described in the prior art.
Ainsi l'invention a pour objet de nouveaux agents édulcorants, caractérisés en ce qu'ils répondent à la formule suivante : Thus the subject of the invention is new sweetening agents, characterized in that they correspond to the following formula:
dans laquelle : in which :
Y est un groupe CH ou un atome d'azote,  Y is a CH group or a nitrogen atom,
A est un atome d'oxygène,  A is an oxygen atom,
n est égal à 1 ou 2, n is 1 or 2,
R est un radical phényle 3,4-disubstitué choisi parmi les groupes :  R is a 3,4-disubstituted phenyl radical chosen from the groups:
et leurs sels physiologiquement acceptables. Les composés de l'invention pour lesquels n est égal à 1 représentent une forme préférée de l'invention. and their physiologically acceptable salts. The compounds of the invention for which n is equal to 1 represent a preferred form of the invention.
Une forme de réalisation particulièrement avantageuse de l'invention est l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-3,4-di thylbenzènamide de formule : A particularly advantageous embodiment of the invention is N- (4-cyanophenylcarbamoyl) -L-aspartic-α-3,4-di thylbenzenamide acid of formula:
dont le pouvoir sucrant, exprimé sur une base pondérale, est 50 000 fois plus élevé que celui du saccharose par comparaison avec une solution de saccharose à 2 %. whose sweetening power, expressed on a weight basis, is 50,000 times higher than that of sucrose compared to a 2% sucrose solution.
Une autre forme de réalisation particulièrement avantageuse de l'invention est l'acide N-(2-cyanopyrid-5- ylcarbamoyl)-L-aspartique-α-3,4-diméthylbenzènamide de formule : Another particularly advantageous embodiment of the invention is N- (2-cyanopyrid-5- acid ylcarbamoyl) -L-aspartic-α-3,4-dimethylbenzenamide of formula:
dont le pouvoir sucrant, exprimé sur une base pondérale, est 40 000 fois plus élevé que celui du saccharose par comparaison avec une solution de saccharose à 2 %. whose sweetening power, expressed on a weight basis, is 40,000 times higher than that of sucrose compared to a 2% sucrose solution.
D'autres composés préférés de l'invention sont caractérisés en ce qu'il s'agit de l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-3,4-méthylènedioxy benzènamide, de l'acide N-(2-cyanopyrid-5-ylcarbamoyl)-L-aspartique-α-3,4-méthylènedioxybenzènamide, de l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-3-hydroxy-4-méthoxybenzènamide, de l'acide N-(2-cyanopyrid-5-ylcarbamoyl)-L-aspartique-α-3-hydroxy-4-méthoxybenzènamide, de l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-3-chloro-4-méthoxybenzènamide, de l'acide N- (4-cyanophénylcarbamoyl)-L-aspart.ique-α-4-mét±yl-3-nitrobenzènamide, de l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-indan-5-ylamide, de l'acide N-(2-cyanopyrid-5-ylcarbamoyl)-L-aspartique-α-indan-5-ylamide, de l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-1,4-benzodioxan- 6-ylamide et de l'acide N-(2-cyanopyrid-5-ylcarbamoyl)-L-aspartique-α-1,4-benzodioxan-6-ylamide.  Other preferred compounds of the invention are characterized in that they are N- (4-cyanophenylcarbamoyl) -L-aspartic-α-3,4-methylenedioxy benzenide, N- acid (2-cyanopyrid-5-ylcarbamoyl) -L-aspartic-α-3,4-methylenedioxybenzenamide, N- (4-cyanophenylcarbamoyl) -L-aspartic-α-3-hydroxy-4-methoxybenzenamide, N- (2-cyanopyrid-5-ylcarbamoyl) -L-aspartic-α-3-hydroxy-4-methoxybenzenamide, N- (4-cyanophenylcarbamoyl) -L-aspartic-α-3-chloro- acid 4-methoxybenzenamide, N- (4-cyanophenylcarbamoyl) -L-aspartic acid-α-4-met ± yl-3-nitrobenzenamide, N- (4-cyanophenylcarbamoyl) -L-aspartic acid- α-indan-5-ylamide, N- (2-cyanopyrid-5-ylcarbamoyl) -L-aspartic acid-α-indan-5-ylamide, N- (4-cyanophenylcarbamoyl) -L- acid aspartic-α-1,4-benzodioxan- 6-ylamide and N- (2-cyanopyrid-5-ylcarbamoyl) -L-aspartic-α-1,4-benzodioxan-6-ylamide acid.
Les composés de l'invention se distinguent donc des composés décrits dans le document JP 86-260052 par la nature très spécifique et la position des substituants fixés sur le groupe benzènamide. En effet, dans ce document antérieur, le cycle benzénique du groupe benzènamide des composés décrits et revendiqués est monosubstitué, et, pour les exemples mentionnés, uniquement en position 4 (para). The compounds of the invention are therefore distinguished from the compounds described in document JP 86-260052 by the very specific nature and the position of the substituents attached to the benzene group. Indeed, in this prior document, the benzene cycle of the benzene group of the compounds described and claimed is monosubstituted, and, for the examples mentioned, only in position 4 (para).
Conformément à la présente invention, le groupe phényle R est simultanément substitué sur les positions 3 (méta) et 4 (para) par des groupes spécifiques. Le choix dans les composés de l'invention de ce nouveau groupe R entraîne une augmentation spectaculaire du pouvoir sucrant, celui-ci pouvant atteindre 10 (dix) fois celui des composés de l'art antérieur, et par conséquent une diminution importante du coût d'utilisation de tels composés.  In accordance with the present invention, the phenyl group R is simultaneously substituted in positions 3 (meta) and 4 (para) by specific groups. The choice in the compounds of the invention of this new group R results in a spectacular increase in the sweetening power, which can reach 10 (ten) times that of the compounds of the prior art, and consequently a significant reduction in the cost of use of such compounds.
Les agents édulcorants de la présente invention peuvent être ajoutés à tout produit comestible dans lequel on désire apporter un goût sucré, à condition de les ajouter en proportions suffisantes pour atteindre le niveau de sucrosité désiré. La concentration optimale d'utilisation de l'agent édulcorant dépendra de facteurs divers tels que, par exemple, le pouvoir sucrant de l'agent édulcorant, les conditions de stockage et d'utilisation des produits, les constituants particuliers des produits et le niveau de sucrosité désiré. Toute personne qualifiée peut facilement déterminer la proportion optimale d'agent édulcorant qui doit être employée pour l'obtention d'un produit comestible en réalisant des analyses sensorielles de routine. Les agents édulcorants de la présente invention seront, en général, ajoutés aux produits comestibles dans des proportions allant, suivant le pouvoir édulcorant du composé, de 0,5 mg à 50 mg d'agent édulcorant par kilogramme ou par litre de produit comestible. Les produits concentrés contiendront évidemment des quantités plus élevées d'agent édulcorant, et seront ensuite dilués suivant les intentions finales d'utilisation.  The sweetening agents of the present invention can be added to any edible product in which it is desired to provide a sweet taste, provided that they are added in sufficient proportions to reach the desired level of sweetness. The optimal concentration of use of the sweetening agent will depend on various factors such as, for example, the sweetness of the sweetening agent, the conditions of storage and use of the products, the particular constituents of the products and the level of desired sweetness. Any qualified person can easily determine the optimal proportion of sweetening agent to be used to obtain an edible product by performing routine sensory analyzes. The sweetening agents of the present invention will, in general, be added to the edible products in proportions ranging, depending on the sweetening power of the compound, from 0.5 mg to 50 mg of sweetening agent per kilogram or per liter of edible product. The concentrated products will obviously contain higher amounts of sweetening agent, and will then be diluted according to the final intentions of use.
Les agents édulcorants de la présente invention peuvent être ajoutés sous forme pure aux produits à édulcorer, mais, en raison de leur pouvoir sucrant élevé, ils sont généralement mélangés à un support ("carrier") ou à un agent de charge ("bulking agent") approprié. Avantageusement, les supports ou agents de charge appropriés sont choisis dans le groupe constitué par le polydextrose, l'amidon, les maltodextrines, la cellulose, la méthylcellulose, la carboxyméthylcellulose et autres dérivés de la cellulose, l'alginate de sodium, les pectines, les gommes, le lactose, le maltose, le glucose, la leucine, le glycérol, le mannitol, le sorbitol, le bicarbonate de sodium, les acides phosphorique, citrique, tartrique, fumarique, benzoïque, sorbique, propionique, et leurs sels de sodium, potassium et calcium, ainsi que leurs équivalents. The sweetening agents of the present invention can be added in pure form to the products to be sweetened, but, because of their high sweetening power, they are generally mixed with a carrier ("carrier") or with a bulking agent ("bulking agent"). ") appropriate. Advantageously, the appropriate carriers or bulking agents are chosen from the group consisting of polydextrose, starch, maltodextrins, cellulose, methylcellulose, carboxymethylcellulose and other derivatives of cellulose, sodium alginate, pectins, gums, lactose, maltose, glucose, leucine, glycerol, mannitol, sorbitol, sodium bicarbonate, phosphoric, citric, tartaric, fumaric, benzoic, sorbic, propionic acids, and their sodium salts , potassium and calcium, and their equivalents.
Les agents édulcorants conformes à l'invention peuvent, dans un produit comestible, être employés seuls, comme unique agent édulcorant, ou en combinaison avec d'autres agents édulcorants tels que le saccharose, le sirop de maïs, le fructose, les dérivés ou analogues dipeptidiques sucrés (aspartame, alitame), la néohespéridine dihydrochalcone, l'isomaltulose hydrogéné, le stévioside, les sucres L, la glycyrrhizine, le xylitol, le sorbitol, le mannitol, l'acésulfame, la saccharine et ses sels de sodium, potassium, ammonium et calcium, l'acide cyclamique et ses sels de sodium, potassium et calcium, le sucralose, la monelline, la thaumatine, ainsi que leurs équivalents.  The sweetening agents in accordance with the invention may, in an edible product, be used alone, as the sole sweetening agent, or in combination with other sweetening agents such as sucrose, corn syrup, fructose, derivatives or the like sweetened dipeptides (aspartame, alitame), neohesperidin dihydrochalcone, hydrogenated isomaltulose, stevioside, sugars L, glycyrrhizin, xylitol, sorbitol, mannitol, acesulfame, saccharin and its sodium salts, potassium, ammonium and calcium, cyclamic acid and its sodium, potassium and calcium salts, sucralose, monellin, thaumatin, and their equivalents.
Les composés de l'invention peuvent aussi être utilisés soit sous leur forme acide soit sous leur forme de sels obtenus à l'aide de bases inorganiques ou organiques physiologiquement acceptables, ce qui a pour effet d'accroître leur solubilité. Avantageusement, ces composés sont salifiés sous forme de sels de sodium, potassium, ammonium, calcium ou magnésium.  The compounds of the invention can also be used either in their acid form or in their salt form obtained using physiologically acceptable inorganic or organic bases, which has the effect of increasing their solubility. Advantageously, these compounds are salified in the form of sodium, potassium, ammonium, calcium or magnesium salts.
La préparation des composés de l'invention met en oeuvre notamment les procédés couramment utilisés pour la synthèse peptidique (voir par exemple M. Bodansky et A. Bodansky, The Practice of Peptide Synthesis, Springer Verlag, Berlin, 1984).  The preparation of the compounds of the invention uses in particular the methods commonly used for peptide synthesis (see for example M. Bodansky and A. Bodansky, The Practice of Peptide Synthesis, Springer Verlag, Berlin, 1984).
La préparation des composés selon l'invention peut ainsi être réalisée à partir de précurseurs d'origine commerciale, comme par exemple l'acide N-benzyloxycarbonyl-L-aspartique β-benzyl ester (n = 1), l'acide N-benzyloxycarbonyl-L-glutamique γ-benzyl ester (n = 2), et l'aminé R-ΝH2 où R est un groupe phényle disubstitue tel que défini précédemment, en suivant le schéma réactionnel suivant : The preparation of the compounds according to the invention can thus be carried out using original precursors commercial, such as N-benzyloxycarbonyl-L-aspartic acid β-benzyl ester (n = 1), N-benzyloxycarbonyl-L-glutamic acid γ-benzyl ester (n = 2), and the amine R -ΝH 2 where R is a disubstituted phenyl group as defined above, following the following reaction scheme:
La purification des composés de l'invention est réalisée selon les techniques standards telles que la recristallisation ou la chromatographie. Leur structure et leur pureté ont été contrôlées par les techniques classiques (chromatographie sur couche mince, chromatographie liquide haute performance, spectrométrie infrarouge, résonance magnétique nucléaire, analyse élémentaire). The purification of the compounds of the invention is carried out according to standard techniques such as recrystallization or chromatography. Their structure and purity have been controlled by conventional techniques (thin layer chromatography, high performance liquid chromatography, infrared spectrometry, nuclear magnetic resonance, elementary analysis).
Le pouvoir édulcorant des composés décrits dans les exemples a été évalué par un groupe de huit personnes expérimentées. Pour cela, les composés, en solution aqueuse à des concentrations variables, sont comparés, sur le plan gustatif, à une solution témoin de saccharose à 2 %. Le pouvoir édulcorant du composé, testé par rapport au saccharose, correspond alors au rapport pondéral qui existe entre le composé et le saccharose à égale intensité édulcorante, c'est-à-dire quand les saveurs sucrées de la solution du composé testé et de la solution témoin de saccharose sont considérées, par une majorité de personnes, avoir la même intensité édulcorante. La manière dont l'invention peut être réalisée et les avantages qui en découlent ressortiront mieux des exemples non limitatifs de réalisation qui suivent. The sweetening power of the compounds described in the examples was evaluated by a group of eight experienced people. For this, the compounds, in aqueous solution at variable concentrations, are compared, in terms of taste, to a 2% sucrose control solution. The sweetening power of the compound, tested relative to sucrose, then corresponds to the weight ratio which exists between the compound and sucrose at equal sweetening intensity, that is to say when the sweet flavors of the solution of the tested compound and of the sucrose control solution is considered, by a majority of people, to have the same sweetening intensity. The manner in which the invention can be carried out and the advantages which result therefrom will emerge more clearly from the nonlimiting examples of embodiment which follow.
EXEMPLES EXAMPLES
Préparation de l'acide N-(4-cyanophénylcarbamoyl)-L- aspartique-α-3,4-diméthylbenzènamide : Preparation of N- (4-cyanophenylcarbamoyl) -L- aspartic-α-3,4-dimethylbenzenamide acid:
1. Préparation de l'acide N-benzyloxycarbonyl-L-aspartique-α-3,4-diméthylbenzènamide β-benzylester : 1. Preparation of N-benzyloxycarbonyl-L-aspartic-α-3,4-dimethylbenzenamide β-benzylester acid:
A une solution de 3 g (8,4 mmoles) d'acide N-benzyloxycarbonyl-L-aspartique β-benzyl ester (produit To a solution of 3 g (8.4 mmol) of N-benzyloxycarbonyl-L-aspartic acid β-benzyl ester (product
Bachem n° C-1350) dans 50 cm3 de tétrahydrofurane refroidie à -15 °C sont successivement ajoutés 0,84 g (8,4 mmoles) de N-méthylmorpholine et 1,14 g (8,4 mmoles) de chloroformiate d'isobutyle. Après 2 minutes d'agitation à cette température, est ajouté 1 g (8,4 mmoles) de 3,4-diméthylaniline (produit Aldrich n° 12,637-3). Le mélange réactionnel est lentement réchauffé puis est agité durant 2 heures à la température ambiante. Le précipité de chlorhydrate de N-méthylmorpholine est éliminé par filtration, puis est lavé par 20 cm3 de tétrahydrofurane. Le filtrat est concentré à sec sous vide et le résidu obtenu est trituré dans 50 cm3 d'éther éthylique. Le solide blanc obtenu est séparé par filtration puis à nouveau lavé par 20 cm3 d'éther éthylique. On obtient ainsi 3,3 g (rendement 85 %) d'acide N-benzyloxycarbony1-L-asparaique-α-3,4-diméthylbenzènamide β-benzylester dont le point de fusion est de 146 °C. 2. Préparation de l'acide L-aspartique-α-3,4-diméthylbenzènamide : Bachem n ° C-1350) in 50 cm 3 of tetrahydrofuran cooled to -15 ° C are successively added 0.84 g (8.4 mmol) of N-methylmorpholine and 1.14 g (8.4 mmol) of chloroformate d 'isobutyle. After 2 minutes of stirring at this temperature, 1 g (8.4 mmol) of 3,4-dimethylaniline (Aldrich product no. 12,637-3) is added. The reaction mixture is slowly warmed up and then stirred for 2 hours at room temperature. The precipitate of N-methylmorpholine hydrochloride is removed by filtration, then is washed with 20 cm 3 of tetrahydrofuran. The filtrate is concentrated to dryness under vacuum and the residue obtained is triturated in 50 cm 3 of ethyl ether. The white solid obtained is separated by filtration and then again washed with 20 cm 3 of ethyl ether. 3.3 g (85% yield) are thus obtained (N-benzyloxycarbony1-L-asparaic-α-3,4-dimethylbenzenamide β-benzylester acid, the melting point of which is 146 ° C.). 2. Preparation of L-aspartic-α-3,4-dimethylbenzenamide:
Une solution de 3 g (5,6 mmoles) d'acide N-benzyloxycarbonyl-L-aspartique-α-3,4-diméthylbenzènamide β-benzylester précédemment obtenu dans 100 cm3 de methanol est soumise, en présence de palladium à 10 % sur charbon actif, à l'hydrogène sous pression atmosphérique durant 18 h. Après élimination du catalyseur par filtration, la solution est concentrée sous vide et le solide blanc obtenu est lavé par trituration dans l'acétone. On obtient ainsi 1,3 g (rendement 85 %) d'acide L-aspartique-α-3,4-diméthylbenzènamide, sous forme d'un solide blanc dont le point de fusion est de 204 °C. Sa pureté est contrôlée par chromatographie sur couche mince sur gel de silice G 60 (support silice Merck n° 1.05554), éluant butanol-acide acétique-eau (8-2-2), révélation à la ninhydrine, Rf = 0,49. A solution of 3 g (5.6 mmol) of N-benzyloxycarbonyl-L-aspartic-α-3,4-dimethylbenzenamide β-benzylester acid previously obtained in 100 cm 3 of methanol is subjected, in the presence of 10% palladium on activated carbon, with hydrogen at atmospheric pressure for 18 h. After removal of the catalyst by filtration, the solution is concentrated under vacuum and the white solid obtained is washed by trituration in acetone. 1.3 g (85% yield) are thus obtained (L-aspartic-α-3,4-dimethylbenzenamide) acid, in the form of a white solid, the melting point of which is 204 ° C. Its purity is checked by thin layer chromatography on G 60 silica gel (Merck silica support n ° 1.05554), eluting butanol-acetic acid-water (8-2-2), revelation with ninhydrin, Rf = 0.49.
3. Préparation de l'acide N-(4-cyayophénylcarbamoyl)-L-aspartique-α-3,4-diméthylbenzènamide :  3. Preparation of N- (4-cyayophenylcarbamoyl) -L-aspartic-α-3,4-dimethylbenzenamide acid:
A une solution de 0,7 g (3 mmoles) d'acide L-aspar ique-α-3,4-diméthylbenzènamide et de 0,63 g To a solution of 0.7 g (3 mmol) of L-asparic acid-α-3,4-dimethylbenzenamide and 0.63 g
(6 mmoles) de carbonate de sodium dans 30 cm3 d'eau, est ajouté, sous agitation vigoureuse, 0,47 g (3,2 mmoles) de 4-cyanophénylisocyanate en solution dans 30 cm3 de benzène. La solution est agitée durant 30 minutes à température ambiante avant d'être lavée par trois fois 30 cm3 d'éther éthylique. L'acidification à pH 2-3 par une solution d'acide chlorhydrique 6 Ν entraîne la formation d'un précipité blanc qui est filtré et lavé par 5-6 cm3 d'eau. Après filtration et séchage, on obtient 0,98 g (rendement 86 %) d'acide N-(4-c4anophénylcarbamoyl)-L- aspartique-α-3,4-diméthylbenzènamide, dont le point de fusion est de 172 °C après recristallisation dans l'éthanol à 95 %. (6 mmol) of sodium carbonate in 30 cm 3 of water, 0.47 g (3.2 mmol) of 4-cyanophenylisocyanate dissolved in 30 cm 3 of benzene is added, with vigorous stirring. The solution is stirred for 30 minutes at room temperature before being washed with three times 30 cm 3 of ethyl ether. Acidification to pH 2-3 with a 6 Ν hydrochloric acid solution results in the formation of a white precipitate which is filtered and washed with 5-6 cm 3 of water. After filtration and drying, 0.98 g (86% yield) of N- (4-c4anophenylcarbamoyl) -L- aspartic acid-α-3,4-dimethylbenzenamide is obtained, the melting point of which is 172 ° C. after recrystallization from 95% ethanol.
Formule moléculaire : C20H20Ν4O4. Molecular formula: C 20 H 20 Ν 4 O 4 .
Chromatographie sur couche mince : gel de silice G 60 F254 sur feuilles d'aluminium (Merck n° 1.05554), éluant : chloroforme - methanol (6:4), révélation à la ninhydrine, Rf = 0,30. Thin layer chromatography: silica gel G 60 F 254 on aluminum sheets (Merck n ° 1.05554), eluent: chloroform - methanol (6: 4), revelation with ninhydrin, Rf = 0.30.
RMN (1H, ppm), DMSO D6 : 2,15 (s, 3H), 2,5 (s, 3H), 2,7 (m, 2H), 4,6 (m, 1H), 6,9 (d, 1H), 7,0 (d, 1H), 7,3 (m, 2H), 7,6 (m, 4H), 9,5 (s, 1H), 9,9 (s, 1H).  NMR (1H, ppm), DMSO D6: 2.15 (s, 3H), 2.5 (s, 3H), 2.7 (m, 2H), 4.6 (m, 1H), 6.9 ( d, 1H), 7.0 (d, 1H), 7.3 (m, 2H), 7.6 (m, 4H), 9.5 (s, 1H), 9.9 (s, 1H).
Chromatographie liquide haute performance sur colonne Merck de type "Lichrospher 100 RP-18 endcapped", longueur 244 mm, diamètre 4,6 mm, éluant : acétate d'ammonium 65 mM - acétonitrile (65:35), débit de 1 ml/min, détecteur : réfractomètre, temps de rétention 13,6 min.  High performance liquid chromatography on a Merck "Lichrospher 100 RP-18 endcapped" column, length 244 mm, diameter 4.6 mm, eluent: 65 mM ammonium acetate - acetonitrile (65:35), flow rate of 1 ml / min , detector: refractometer, retention time 13.6 min.
L'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α- 3,4-diméthylbenzènamide a un pouvoir sucrant qui est, sur une base pondérale, 50 000 fois plus élevé que celui du saccharose par comparaison avec une solution de saccharose à 2 % . N- (4-cyanophenylcarbamoyl) -L-aspartic-α- 3,4-dimethylbenzenamide has a sweetening power which is, on a weight basis, 50,000 times higher than that of sucrose compared to a sucrose solution at 2%.
A titre d'exemples, le pouvoir sucrant d'autres composés selon l'invention, obtenus suivant un protocole expérimental similaire à celui décrit ci-dessus et que l'homme de l'art retrouvera facilement, est donné dans le Tableau 1. Les pouvoirs sucrants approximatifs, exprimés en valeurs arrondies, sont donnés comparativement à une solution de saccharose à 2 %. By way of examples, the sweetening power of other compounds according to the invention, obtained according to an experimental protocol similar to that described above and which those skilled in the art will easily find, is given in Table 1. The approximate sweetness values, expressed in rounded values, are given compared to a 2% sucrose solution.

Claims

REVENDICATIONS
1. Composés édulcorants caractérisés en ce qu'ils répondent à la formule suivante : 1. Sweetening compounds characterized in that they correspond to the following formula:
dans laquelle : in which :
Y est un groupe CH ou un atome d'azote,  Y is a CH group or a nitrogen atom,
A est un atome d'oxygène,  A is an oxygen atom,
n est égal à 1 ou 2, n is 1 or 2,
R est un radical phényle 3,4-disubstitué choisi parmi les groupes :  R is a 3,4-disubstituted phenyl radical chosen from the groups:
et leurs sels physiologiquement acceptables. and their physiologically acceptable salts.
2. Composés édulcorants selon la revendication 1 caractérisés en ce que n est égal à 1. 2. Sweetening compounds according to claim 1 characterized in that n is equal to 1.
3. Composé édulcorant selon la revendication 1 caractérisé en ce qu'il s'agit de l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-3,4-diméthylbenzènamide de formule : 3. Sweetener compound according to claim 1 characterized in that it is N- (4-cyanophenylcarbamoyl) -L-aspartic-α-3,4-dimethylbenzenamide acid of formula:
4. Composé édulcorant selon la revendication 1 caractérisé en ce qu'il s'agit de l'acide N-(2-cyanopyrid-5-ylcarbamoyl)-L-aspartique-α-3,4-diméthylbenzènamide de formule :  4. Sweetener compound according to claim 1 characterized in that it is N- (2-cyanopyrid-5-ylcarbamoyl) -L-aspartic-α-3,4-dimethylbenzenamide acid of formula:
5. Composés édulcorants selon les revendications 1 et 2 caractérisés en ce qu'il s'agit de l'acide N- ( 4 -cyanophénylcarbamoyl)-L-aspartique-α-3,4-méthylènedioxy benzènamide, de l'acide N-(2-cyanopyrid-5-ylcarbamoyl)-L-aspartique-α-3,4-méthylènedioxybenzènamide, de l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-3-hydroxy-4-méthoxybenzènamide, de l'acide N-(2-cyanopyrid-5-ylcarbamoyl)-L-aspartique-α-3-hydroxy-4-méthoxybenzènamide, de l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-3-chloro-4-méthoxybenzènamide, de l'acide N-(4-cyano phénylcarbamoyl)-L-aspartique-α-4-méthyl-3-nitrobenzènamide, de l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-indan-5-ylamide, de l'acide N-(2-cyanopyrid-5-ylcarbamoyl)-L-aspartique-α-indan-5-ylamide, de l'acide N-(4-cyanophénylcarbamoyl)-L-aspartique-α-1,4-benzodioxan-6-ylamide et de l'acide N-(2-cyanopyrid-5-ylcarbamoyl)-L-aspartique-α-1,4-benzodioxan-6-ylamide. 5. Sweetening compounds according to claims 1 and 2 characterized in that it is N- (4-cyanophenylcarbamoyl) -L-aspartic-α-3,4-methylenedioxy acid benzene, N- (2-cyanopyrid-5-ylcarbamoyl) -L-aspartic-α-3,4-methylenedioxybenzenamide, N- (4-cyanophenylcarbamoyl) -L-aspartic-α-3- hydroxy-4-methoxybenzenamide, N- (2-cyanopyrid-5-ylcarbamoyl) -L-aspartic-α-3-hydroxy-4-methoxybenzenamide, N- (4-cyanophenylcarbamoyl) -L- acid aspartic-α-3-chloro-4-methoxybenzenamide, N- (4-cyano phenylcarbamoyl) -L-aspartic-α-4-methyl-3-nitrobenzenamide, N- (4-cyanophenylcarbamoyl) acid -L-aspartic-α-indan-5-ylamide, N- (2-cyanopyrid-5-ylcarbamoyl) acid -L-aspartic-α-indan-5-ylamide, N- (4- cyanophenylcarbamoyl) -L-aspartic-α-1,4-benzodioxan-6-ylamide and N- (2-cyanopyrid-5-ylcarbamoyl) -L-aspartic-α-1,4-benzodioxan-6-ylamide acid .
6. Composition édulcorante caractérisée en ce qu'elle contient au moins un des composés édulcorants selon l'une quelconque des revendications 1 à 5. 6. Sweetening composition characterized in that it contains at least one of the sweetening compounds according to any one of claims 1 to 5.
7. Application des composés selon l'une quelconque des revendications 1 à 5 comme agents édulcorants. 7. Application of the compounds according to any one of claims 1 to 5 as sweetening agents.
8. Procédé de préparation des composés selon l'une quelconque des revendications 1 à 5 caractérisé en ce qu'il consiste à condenser un composé de formule : 8. A process for preparing the compounds according to any one of claims 1 to 5, characterized in that it consists in condensing a compound of formula:
avec un composé de formule : : with a compound of formula::
dans lesquelles n, R et Y sont tels que définis dans la revendication 1. wherein n, R and Y are as defined in claim 1.
EP96901851A 1995-01-26 1996-01-25 NOVEL SWEETENERS DERIVED FROM 3,4-DISUBSTITUTED $g(a)-BENZENEAMIDE N-(4-CYANOPHENYLCARBAMOYL OR 2-CYANOPYRID-5-YLCARBAMOYL)-L-ASPARTIC OR L-GLUTAMIC ACIDS Withdrawn EP0805799A1 (en)

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FR9500878A FR2729950B1 (en) 1995-01-26 1995-01-26 NOVEL SWEETENING AGENTS DERIVING N- (4- CYANOPHENYLCARBAMOYL OR 2-CYANOPYRID-5-YLCARBAMOYL) -L- ASPARTIC OR L-GLUTAMIC ALPHA-BENZENAMIDES
FR9500878 1995-01-26
PCT/FR1996/000124 WO1996022971A1 (en) 1995-01-26 1996-01-25 NOVEL SWEETENERS DERIVED FROM 3,4-DISUBSTITUTED α-BENZENEAMIDE N-(4-CYANOPHENYLCARBAMOYL OR 2-CYANOPYRID-5-YLCARBAMOYL)-L-ASPARTIC OR L-GLUTAMIC ACIDS

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EP0805799A1 true EP0805799A1 (en) 1997-11-12

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EP96901851A Withdrawn EP0805799A1 (en) 1995-01-26 1996-01-25 NOVEL SWEETENERS DERIVED FROM 3,4-DISUBSTITUTED $g(a)-BENZENEAMIDE N-(4-CYANOPHENYLCARBAMOYL OR 2-CYANOPYRID-5-YLCARBAMOYL)-L-ASPARTIC OR L-GLUTAMIC ACIDS

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EP (1) EP0805799A1 (en)
JP (1) JPH10512872A (en)
AU (1) AU689698B2 (en)
CA (1) CA2209922A1 (en)
FR (1) FR2729950B1 (en)
WO (1) WO1996022971A1 (en)

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Publication number Priority date Publication date Assignee Title
FR2744122B1 (en) * 1996-01-25 1998-04-30 Univ Claude Bernard Lyon NOVEL SWEETENING AGENTS DERIVING N- (4-CYANOPHENYLCARBAMOYL OR 2-CYANOPYRID-5-YLCARBAMOYL) -L- ASPARTIC ALPHA-BENZENAMIDE 3-MONOSUBSTITUTE ACID
NZ507938A (en) * 1998-04-09 2002-11-26 Ajinomoto Kk Aspartyl dipeptide ester derivatives and sweeteners
JP2020055751A (en) * 2017-02-13 2020-04-09 味の素株式会社 Novel compound and taste-improving agent containing that compound

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Publication number Priority date Publication date Assignee Title
JPS61260052A (en) * 1985-05-14 1986-11-18 Ajinomoto Co Inc Novel amino acid derivative and sweetener
AU636853B2 (en) * 1988-08-23 1993-05-13 Nutrasweet Company, The Substituted aryl ureas as high potency sweeteners

Non-Patent Citations (1)

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Title
See references of WO9622971A1 *

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CA2209922A1 (en) 1996-08-01
FR2729950A1 (en) 1996-08-02
AU689698B2 (en) 1998-04-02
FR2729950B1 (en) 1997-04-18
WO1996022971A1 (en) 1996-08-01
JPH10512872A (en) 1998-12-08
AU4626796A (en) 1996-08-14

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