MXPA01002402A - N-alkylaspartyldipeptide ester derivatives and sweeteners - Google Patents

Abstract

Novel N-alkylaspartyldipeptide ester derivatives (involving those in the form of a salt) such as N-[N-[3- (3-hydroxy -4 -methoxyphenyl) -3-methylbutyl]-L -&agr;-aspartyl]-L-henylalanine 1-methyl ester which are usable as excellent sweeteners. Because of having low caloric values and being superior in the degree of sweetness to the conventional ones, these derivatives make it possible to provide sweeteners, foods, etc. containing the same.

Description

DERIVATIVE DIPEPTIDQ ESTER OF N-RENTALS AND EDULCORANT AGENT DESCRIPTION OF THE INVENTION This invention relates to a novel N-alkylapartyl dipeptide ester derivative, a sweetening agent or a sweetened food or the like product comprising the derivative as an effective component. In recent years, as eating habits have been improved to a high level, obesity caused by excessive intake of sugar and diseases accompanied by obesity have been the subject. Therefore, the development of a low calorie sweetness (sweetening agent) that replaces sugar has been in demand. As a Sweetness that has been widely used in the present, there is aspartame which is excellent in safety and quality of sweetening. However, this is somewhat problematic in stability. In International Patent Publication WO 94/11391 it is stated that derivatives in which an alkyl group is introduced into a nitrogen atom of aspartic acid constituting aspartame are markedly improved in the sweetening potency and are slightly improved in stability. Of the compounds set forth in this publication, the N- [N- (3,3- dimethylbutyl) -L-α-aspartyl] -L-phenylalanine 1-methyl ester which has introduced the 3, 3-dimethylbutyl group as a group I rent It is more excellent. The sweetening potency of this compound is reported to be 10,000 times that of sucrose, which is a value obtained in comparison to the previous compound at 2% -, 5% - and 10% - of the sucrose solution. There are also established aspartame derivatives that have 20 types introduced from other substituents of the 3,3-dimethylbutyl group. The sweetening potency of these aspartame derivatives was reported to be no higher than 2500 times that of sucrose. There are also established aspartame derivatives having a 3- (substituted phenyl) propyl group introduced as an alkyl group. Among these, N- [N- (-phenylpropyl) -La-aspartyl] -L-phenylalanine 1-methyl ester and N- [N- (3- (3-methoxy-4-hydroxyphenylpropyl) 1-methyl ester - La-aspartyl] -a-phenylalanine, as derivatives that have relatively high sweetening potency, were reported to have the sweetening potency of 1500 and 2500 times that of sucrose, respectively, however, the sweetening potency of these derivatives is much lower that of the N- [N- (3,3-dimethylbutyl) -L-aspartyl] -L-phenylalanine 1-methyl ester, which is 10000 times that of sucrose, and also N-1-methyl ester N- [(RS) -3-phenylbutyl] -la-aspartyl] -L-phenylalanine, having as an alkyl group, a substituent corresponding to the 3-phenylpropyl group, in the third position of which a methyl group is additionally introduced , which is a 3-phenylbutyl group, is reported to have a sweetening potency of 1200 times that of sucrose, it is slightly lower in sweetening potency in Comparison with N- [N- (3-phenylpropyl) -L-a-aspartyl] -L-phenylalanine 1-methyl ester due to the methyl group introduced to the third position. On the other hand, the 1-methyl ester of N- [N- [3- (3-methoxy-4-hydroxyphenyl) - (RS) -1-methylpropyl] -La-aspartyl] -L-phenylalanine having a corresponding structure to N- [N- [3- (3-methoxy-4-hydroxyphenyl) propyl] -L-α-aspartyl] -L-phenylalanine 1-methyl ester, to the first position of the propyl group from which a methyl group is introduced, is reported to have a sweetening power 500 times that of sucrose. This derivative is significantly lower in its sweetening potency due to the methyl group introduced to the first position of the propyl group. As an example of the methyl ester of the substitution of the methyl ester portion of L-phenylalanine with another amino acid ester, there is the established 1-methyl ester N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-tyrosine. This derivative was reported to have a sweetening potency 4000 times that of sucrose. In view of the state described above in the art, a low calorie sweetening agent development having superior sweetening potency has been required. Problem to be solved by the Invention It is a problem to be solved by the present invention to provide a novel N-alkylapartyl dipeptide ester derivative having a sweetening potency equivalent to or greater than that of N- [N- [3] -dimethylbutyl] -La-aspartyl-L-phenylalanine described above, and a low calorie sweetening agent comprising the derivative as an effective component (ingredient). To solve the above problem, the present inventors have synthesized a variety of compounds in which a variety of 3- (substituted phenyl) propyl group, such as 3, 3-dialkyl-3- (substituted phenyl) propyl groups or groups (RS ) -3-alkyl-3- (substituted phenyl) propyl, have been introduced into a nitrogen atom of an aspartic acid constituting an aspartame and an aspartame derivative, by reductive alkylation, using a 3-phenylpropionaldehyde derivative, a cinnamaldehyde derivative, a (2-phenylethyl) alkyl ketone derivative or the like having a variety of substituents on a phenyl group and also having 1 to 4 alkyl substituents on the main chain, and examining the sweetening potency of these derivatives. The aspartame derivative is a compound corresponding to the aspartame of the methyl ester portion of L-phenylalanine, of which it is substituted by another amino acid ester herein. As a result of our research, the sweetening potency of some of the aspartame derivatives , && amp; * •• it is much higher in sweetening potency than the N- [N- (3, 3-d? methyl-butyl) -La-aspartyl] -L-phenylalanine 1- methyl ester reported to have the sweetening power of 10,000 times that of sucrose , to say nothing of the N- [N- [(RS) -3-phenylbutyl] -L-aspartyl] -L-phenylalanine methyl ester reported to have a sweetening potency equal to 4000 times that of sucrose, as was described in International Patent Publication WO 94/11391, and that, in particular, the compound represented by the formula The following general (1) is superior as a sweetening agent. The present invention has been brought to the conclusion based on these findings. That is, the present invention resides in a N-alkylapartyl dipeptide ester derivative, inclusive of its salt form, and a sweetening agent or sweetened food or similar product comprising the derivative, wherein the derivative is represented by the following general formula (1): In the above formula, Rx, R2, R3, R4 and R5 are reciprocally independent and denote a substituent selected from the group consisting of a hydrogen atom, a hydroxyl group, an alkoxy group having 1 to 3 carbon atoms , an alkyl group having from 1 to 3 carbon atoms and a hydroxyalkyloxy group having from two to three carbon atoms, or Ri and R2, or R2 and R are combined together and mean a methylenedioxy group. In the case where Ri and R2, or R2 and R3 combined together mean a methylenedioxy group, R and R5 and Ri or R3 which are not combined together with R2, are reciprocally independent and denote one of the aforementioned substituents designated by the symbol . Rβ, R, Rs, Rg and Rio are reciprocally independent and denote a substituent selected from the group consisting of a hydrogen atom and an alkyl group with 1 to 3 carbon atoms and optionally two substituents selected from R5, R7, Rs , R9 and Rio here can be combined together and mean an alkylene group with 1 to 5 carbon atoms. If any of the two optional substituents selected from Rβ, R, Rs, R9 and Rio combined together mean an alkylene group with 1 to 5 carbon atoms, the substituents different from the two selected substituents are reciprocally independent and denote one of the previously defined substituents designated respectively by the symbol. In the previous formula, the connections indicated by wavy lines are simple connections, without being limitations in the direction of the connection. If R and R7, or R8 and Rg mean different substituents, or if Rio means a substituent different from a hydrogen atom, there is no limitation in the configuration of the carbon atoms to which R and R are attached, those to which Rs and Rg are united or those to which Rio is linked. For example, these configurations can be (R), (s) or (RS) independently of each other. Rn means a substituent selected from the group consisting of a hydrogen atom, a benzyl group, a p-hydroxybenzyl group, a cyclohexylmethyl group, a phenyl group, a cyclohexyl group, a phenylethyl group and a cyclohexylethyl group, and Ri2 means a substituent selected from the group consisting of a hydrogen atom and an alkyl group with 1 to 3 carbon atoms, and R? means a substituent selected from the group consisting of an alkyl group with 1 to 4 carbon atoms. However, the derivatives in which Rβ, R, Rs, Rg and Rio in their entirety mean a hydrogen atom a jL * At¡ £ *.? > -i * .Í * »* ~ - í. **? A.tA **. ttt * i *? *? *? lt? *? i? tS * n¡ this same time, those in which R means a methyl group, Ri, R2, R3, R, R5, R7, Rs, R9, Rio, and R12 means a hydrogen atom at the same time and Ru means a benzyl group or a p-hydroxybenzyl group at the same time, and those in which R2 signifies a methoxy group, R3 signifies a hydroxyl group, Rio signifies a methyl group, Ri, R, R5, R, R7, Rs and R9 signifies a hydrogen atom at the same time, and Ru signifies a group benzyl or a p-hydroxybenzyl group are excluded from the derivatives described above. Modes for Carrying Out the Invention The novel N-alkylaspartyl dipeptide ester derivative according to the present invention includes compounds represented by the above formula (1) and also salts formed therefrom. Of the amino acids that constitute the above derivative, aspartic acid is in the L-isomer. Other amino acids may be in the L- or D isomer, as desired. The compounds of the present invention preferably include the following compounds: [1] The compounds represented by the aforementioned formula (1); with the condition that, in the previous formula (1), Ri, R2, R3, R4, and R5 are each independently and means a substituent selected from the group - ?? t? -? *, * ^ * * ** consisting of a hydrogen atom (H), a hydroxyl group (OH), an alkoxy group with 1 to 3 carbon atoms (OCH3 OCH2CH3, OCH2CH2CH3 and things like that), an alkyl group with 1 to 3 carbon atoms (CH3, CH2CH3, CH2CH2CH3 and the like), a hydroxyalkyloxy group with two or three carbon atoms (0 (CH2) 2OH, OCH2CH (OH) CH3 and the like) or Ri and R2, or R2 and R here combine together and mean a methylenedioxy group (OCH20). It was observed that in the case where Ri and R2 or R2 and R3 combined together mean a methylenedioxy group, R and R5 and Ri or R3 which do not combine with R are reciprocally independent from each other and means one of the aforementioned substituents designated respectively by the symbol. R6, R, Rs, Rg and Rio are reciprocally independent of each other and means a substituent selected from the group consisting of a hydrogen atom and an alkyl group with 1 to 3 carbon atoms and optionally two substituents selected from from R6, R7, R8, Rg and Rio combine together and mean an alkyl group with 1 to 5 carbon atoms (such as CH2, CH2CH2, CH2CH2CH2 and the like). In the case where the two optimum substituents selected from the group consisting of R6, R, Rs, Rg and Rio combined together mean an alkylene group with 1 to 5 carbon atoms, the remaining substituents are reciprocally independent of each other and means the respective specific or illustrated substituents designated respectively by the symbol. In the previous formula (), a connection denoted by a wavy line is a unique connection, without limitations being in the direction of the connection. In the case where R6 and R or R8 and Rg mean different respective substituents of each other, or Rio is a substituent different from a hydrogen atom, there is no limitation to the configuration of the carbon atom to which Rg and R are link, a carbon atom to which Rs and R9 are linked or a carbon atom to which Rio is bound. Thus, the configuration can be any of (R), (S), (RS) or the like. Rn means a substituent selected from the group consisting of a hydrogen atom, a benzyl group (CH2C6H5), a p-hydroxybenzyl group (CH2CeH5-p-0H), a cyclohexylmethyl group (CH2C6Hp), a phenyl group (C6Hs) , a cyclohexyl group (C6Hu), a phenylethyl group (CH2CH2C6H5) and a cyclohexylethyl group (CH2CH2C6Hu), and Ri2 means a substituent selected from the group consisting of a hydrogen atom and an alkyl group with 1 to 3 carbon atoms , and Ri3 means a substituent selected from the group consisting of alkyl groups with 1 to 4 carbon atoms. carbon. However, the derivatives in which Re, R7, Rs, Rg and Rio in their entirety mean a hydrogen atom at the same time, those in which Rβ signifies a methyl group, Ri, R2, R3, R4, R5, R7, Rs, R9, Rio and R12 means a hydrogen atom at same time and Rn means a benzyl group or a p-hydroxybenzyl group at the same time, and those in which R2 means a methoxy group, R3 means a hydroxyl group, Rio means a methyl group, Ri, R4, R5, R6, R7 , R8 and Rg mean a hydrogen atom at the same time, and Rn means a benzyl group or a p-hydroxybenzyl group, are excluded from the derivatives. [2] The compound as defined in [1] wherein Rg is a methyl group- [3] The compound as defined in [2] wherein R is a methyl group. [4] The compound as defined in [3] wherein R8, Rg and Rio are hydrogen atoms. [5] The compound as defined in [1] to [3], where Rio is a methyl group. [6] The compound as defined in [1] wherein R and R7 combine together and mean an alkylene group having from 1 to 5 carbon atoms. [7] The compound as defined in [2] except the compound where all of Rx, R2, R3, R4 and R5 mean a hydrogen atom. [8] The compound as defined in [1] where R6 is a methyl group and Rx, R2, R3, R4, Rs, R7, Rs, R9 and Rio are all hydrogen atoms. [9] The compound as defined in [1] wherein Rβ is an alkyl group having two or three carbon atoms. [10] The compound as defined in [1] wherein any two optional substituents are selected from R6, R7, Rs, R9 and Rio combined together means an alkylene group with one to five carbon atoms. [11] The compound as defined in [1] wherein Rβ, R, Rs, Rg are all hydrogen atoms, Rio is a methyl group, R 2 is a substituent selected from a hydrogen atom, a hydroxyl group, a group alkoxy with two or three carbon atoms, an alkyl group with one to three carbon atoms and a hydroxyalkyloxy group having two or three carbon atoms, or R2 combined with Rt or R3 means a methylenedioxy group. [12] The compound as defined in [1] wherein Rβ, R, R8 and Rg are all hydrogen atoms, Rio is a methyl group, R3 is a substituent selected from a hydrogen atom, an alkoxy group with one to three carbon atoms, an alkyl group having one to three carbon atoms and a hydroxyalkyloxy group having two or three carbon atoms, and R2 can be combined with Ri or R3 to form a Methylenedioxy group. [13] The compound as defined in [1] wherein Ri, R4, R5, R6, R7, R8, and Rg are all hydrogen atoms, Ri0 is a methyl group, R2 is a methoxy group, R3 is a hydroxyl group , and Ru is a substituent selected from the group selected from the group consisting of a hydrogen atom, a cyclohexylmethyl group, a phenyl group, a cyclohexyl group, a phenylethyl group (CH2CH2C6H5) and a cyclohexylethyl group (CH2CH2C6Hn). [14] The compound as defined in [1] wherein R6 and R means hydrogen atoms and Rio is an alkyl group with two or three carbon atoms. [15] The compound as defined in [1] wherein R6 and R7 signifies hydrogen atoms and two optional selected from R8, Rg and Rio are combined together and mean an alkylene group with 1 to 5 carbon atoms. [16] Compounds as defined in [1] wherein Rβ, R7 and Rio means hydrogen atoms, at least one of R3 and Rg mean an alkyl group with one to three carbon atoms or Rs and R9 are combined together and they mean an alkylene group with 1 to 5 carbon atoms. [17] The derivative in [1] where R3 signifies a methoxy group, Ri, R2, R4, R5, R7, R8, Rg, Rio and R12 mean hydrogen atoms, Re and R13 mean a methyl group and Ru means a group benzyl

[18] E derivative in [1] wherein R2 is a hydroxyl group, Rx, R3, R4, R5, R7, Rs, Rg, Rio and R12 signify a hydrogen atom, R6 and R13 signify a methyl group,, and R means a benzyl group. [19] The derivative in [1] wherein R2 is a methoxy group, R3 is a hydroxyl group, Ri, R4 R5, R7, Rs, R9, Rio and R12 mean a hydrogen atom, R6 and R13 mean a methyl group and Rn mean a benzyl group. [20] The derivative in [1] wherein R2 is a hydroxyl group, R3 is a methoxy group, Ri, R4, R5, R7 R8, R9, Rio and RX2 means a hydrogen atom, Rβ and R13 mean a methyl group and Rn means a benzyl group. [21] The derivative in [1] wherein R2 is a methoxy group, R3 is a hydroxyl group, Ri, R4, R5, R8, Rg, Rio and R12 signify hydrogen atoms, R6 and R13 signify a methyl group and Rn means a p-hydroxybenzyl group. [22] The derivative in [1] wherein R2 is a hydroxyl group, R3 signifies a methoxy group, Ri, R4, R5, R7, R8, R9 Rio and R12 signify a hydrogen atom, Rβ and R13 signify a methyl group and Rn means a cyclohexylmethyl group. [23] The derivative in [1] wherein R3 is a methoxy group, Ri, R2, R, R5, R6, Rg, Rio and R12 signify a hydrogen atom, R6, R7 and R13 signify a methyl group, and Rn they mean a benzyl group. [24] The derivative in [1] where R3 is a group hydroxyl, Rx, R2, R4, R5, Rs, Rg, Rio and R12 signify a hydrogen atom, Re, R7 and R13 signify a methyl group and R signifies a benzyl group. [25] The derivative in [1] wherein R2 is a methoxy group, R3 is a hydroxyl group, Ri, R4, R5, R8, Rg, Rio and R12 signify a hydrogen group Rβ, R7 and R13 mean a methyl group and Rn mean a benzyl group. [26] The derivative in [1] wherein R2 is a hydroxyl group, R3 is a methoxy group, Ri, R4, R5, Rs, R9, Rio and R12 signify a hydrogen group, Rβ, R7 and R13 mean a methyl group and Rn mean a benzyl group. [27] The derivative in [1] wherein R2 is a methyl group, R3 signifies a hydroxyl group, Ri, R4, R5, R7, Rs, R9, Rio and R12 signifies a hydrogen atom, R6 and 13 signifies a group methyl and Rn means a benzyl group. [28] The derivative in [1] wherein R2 is a hydroxyl group, R3 signifies a methoxy group, Ri, R4, R5, Rβ, R7, R9, Rio and R12 signify a hydrogen atom, R8 and Ri3 signify a group methyl and Rp means a benzyl group. [29] The derivative in [1] wherein Ri is a hydroxyl group, R2, R3, R4, R5, R8, Rg, Rio and R12 means a hydrogen atom, Re, R7 and R13 mean a methyl group and Rn means a benzyl group. [30] The derivative in [1] wherein Ri is a hydroxyl group, R3 is a methoxy group, R2, R4, R5, R8, Rg, Rio and R12 '? & *** A *? s ~ * £. £ *. ** áL-. *** A, * & jt ,? .? a &** ** i ** f &tíit? j * ±? M **. they mean a hydrogen atom, R6, R7 and R13 mean a methyl group and Rn means a benzyl group. [31] The derivative in [1] wherein Ri is a hydroxyl group, R3 is a methyl group, R2, R4, R5, Rs, R9, Rio and R12 5 mean a hydrogen atom, R6, R7 and R13 mean a methyl group and Rn means a benzyl group. [32] The derivative in [1] wherein R2 and R3 combine together and mean a methylenedioxy group, Ri, R4, R5, R8, Rg, Rio and R12 mean a hydrogen atom, R6, R7 and R13 10 mean a methyl group and Ru is a benzyl group. [33] The derivative in [1] wherein R2 signifies a methyl group, R3 signifies a methoxy group, Ri, R4, R5, Rs, R9, Rio and R12 signify a hydrogen atom, Rβ, R7 and R13 signify a group methyl and Rn means a benzyl group. [34] The derivative in [1] wherein R2 means a methyl group, R3 is a hydroxyl group, Ri, R, R5, R8, Rg, Rio and RX2 mean a hydrogen atom, Rβ, R7 and R13 mean a methyl group, and Rn means a benzyl group. [35] The derivative in [1] wherein R2 signifies a hydroxyl group, R3 signifies a methyl group, Ri, R4, R5, Rs, R9, Rio and R12 signify a hydrogen atom, R6, R7 and R13 signify a methyl group and Rn means a benzyl group. [36] The derivative in [1] wherein R2 signifies a methoxy group, R3 signifies a hydroxyl group, Ri, R4, R5, R8, Rg, R10 and R? 2 mean a hydrogen group, R? And R7 are they combine together and signify a tetramethylene group, Rn signifies a benzyl group and Ri3 signifies a methyl group. [37] The derivative in [1] wherein R2 signifies a hydroxyl group, R3 signifies a methoxy group, Ri, R4, R5, Rs, R19 and R12 signify a hydrogen atom, and R7 signifies a methyl group, Rn means a Benzyl group and R13 means an ethyl group. [38] The derivative in [1] wherein R2 and R3 signify a hydroxyl group, Ri, R4, R5, R8, R9, Rio and R12 signify a hydrogen atom R, R7 and R13 signify a methyl group, and Rn means a benzyl group. [39] The derivative in [1] wherein R2 is a hydroxyl group, R3 signifies a methoxy group, Ri, R, R5, R8, R9 and Rio signify a hydrogen atom, Rβ, R7, R12 and R12 signify a group methyl and Rn means a benzyl group. [40] The derivative in [7] to [22] and [27] wherein the configuration of the carbon atom to which R8 is bound in the formula is in the form of (R), (S), (RS) or the similar ones. [41] The derivative in [28] wherein the configuration of the carbon atom to which R8 is bound in the formula is in the form of (R), (S), (RS), or the like. [42] The derivative in [1] where the configuration of the carbon atom to which Rio is bound in the formula is in the form of (R), (S), (RS) or the like.

For preferred embodiments, the following inventions were contained in the present invention. [43] A sweetening agent or a sweetened food or the like product comprising the derivative defined above in the present invention as an effective component, which may occasionally contain a carrier and / or bulking agent. [44] A method for imparting sweetness, comprising a step of: giving (mixing or adding) the above derivative to a product in need of sweetness, such as food, drink (beverages), pharmaceutical and oral hygiene products, and products that they require sweetness for animals other than humans. [45] A method for manufacturing a compound represented by the above general formula (1), wherein Rio means a hydrogen atom, such a method comprising a step of reacting an aldehyde shown by the following general formula (2): wherein Rx, R2, R3, R4, R5, R, R7, Rs and R9 have the same meaning as Ri, R2, R3, R, Rs, Rs, R7, Rs and R9 respectively in the previous formula (1); It being noted that the connections denoted by wavy lines in the above formula (2) are simple connections without limitations being in the connection direction; being also observed that, if R R? , or R8 and R9 are not the same substituents, there is no particular limitation to the configuration of carbon atoms to which R and R7, or Rs and Rg are linked, such that they can be (R), (S), (RS) or any similar is desired; with an aspartame derivative shown by the following general formula (3): under a condition of reductive alkylation; wherein Ru, R12 and R13 in the above formula (3) '"have the same meaning as Rn, R? 2 and Rx3, respectively in the above formula (1), R14 means a hydrogen atom or a substituent which can be converted to a hydrogen atom under the condition of reductive alkylation and R15 means a hydrogen atom, a benzyl group or a substituent which can be used to protect a carboxyl group such as a t-butyl group or the Similar . [46] A method for manufacturing a compound represented by the above general formula (1), wherein R7, Rg and Rio signify a hydrogen atom, the method comprising a step of reacting an aldehyde shown by the following general formula (4) ) where R? f R3, R4 Rs, Re and Rs have the same meaning as Rl R2, R3, R4, Rs, Rs and Rs, respectively in the above formula (1); with an aspartame derivative shown by the aforementioned generating formula (3) under a reductive alkylation condition. [47] A method for manufacturing a compound represented by the above general formula (1), comprising a step of reacting an aldehyde shown by the following general formula (5) where Rx, R2, R3, R4, R5, Re, R7, Rs, Rg and Rio have the same meanings as Ri, R2, R3, R4, R5, Re, R7, Rs, Rs and Rio, respectively in the previous formula (1); it being noted that the connections denoted by wavy lines in the above formula (5) are simple connections, without limitations being in the direction of the connection; it being also noted that, if R6 and R7 or R8 and R9 are not the same substituents, there is no particular limitation on the configuration of the carbon atoms to which R6 and R7, or R8 and Rg are linked, such as ( R), (S), (RS) or any similar one is desired; with the aspartame derivative shown by the following general formula above (3) under a reductive alkylation condition. It is sufficient if the manufacturing methods given in [45] to [47] include the reaction step under the condition of reductive alkylation, such as a different step or stages of the reaction step under the condition of reductive alkylation can also be included in the manufacturing method. They can also be included in an optional step or stages, following the reaction step under the condition of reductive alkylation, for example, deprotection in a hydroxyl group or the other functional group, a salt forming step or the like, to *. * « produce such objective compounds. As the substituent that can be converted to a hydrogen atom or the reductive dealkylation condition, those that can usually be used for such purposes, such as benzyloxycarbonyl group or the like, can optionally be selected depending on the particular reductive alkylation condition used . As those reductive alkylation conditions, conditions as known per se, or any suitable conditions that will be developed in the future, such as a condition using metal hydrides, may be used, as necessary. As a further preferable present embodiment of the present invention, if the aldehyde shown by the general formulas (2), (4) or (5) include hydroxyl groups, the manufacturing methods described above of [45] to [47] employing a aldehyde the hydroxyl group of which is protected by a suitable protecting group, such as benzyl group, may also be contained in the present invention. It was observed that the salts of the compounds of the present invention, which are included in the derivatives of the present invention, can be listed by, for example, alkali metal salts such as sodium and potassium, alkaline earth metal salts, such as calcium and magnesium, ammonium salt with ammonia, salts with amino acids, such as lysine and arginine, acids with inorganic acids, such as acid chloride and sulfuric acid, salts with organic acids, such as citric acid and acetic acid, and salts with sweetening agents, such as saccharin, acesulfame, cyclamic acid and glycyrhizic acid. These salts may be included in the derivatives of the present invention, as noted above. The N-alkylaspartyl dipeptide ester derivative of the present invention which can be easily synthesized by reductive alkylation of aspartame or aspartame derivatives, which are compounds obtained by replacing one portion of L-phenylalanine methyl ester in aspartame with another amino acid ester, using a 3-phenylpropionaldehyde derivative, a cinnamaldehyde derivative or a (2-phenylethyl) alkyl ketone derivative, having different substituents in the main chain, and a reducing agent, such as an acid / palladium carbon catalyst. Alternatively, the N-alkylapartyl dipeptide ester derivative of the present invention can be produced by a method consisting of reductive alkylation of an aspartame derivative, having a protecting group in a β position in the carboxylic acid, such as methyl ester of β-acid. -O-benzyl-aL-aspartyl-L-amino, using the 3-phenylpropionaldehyde derivative described above, a derivative cinnamaldehyde or a derivative (2-phenylethyl) alkyl ketone, and a reducing agent, such as NaB (0Ac) 3H, as described in A. F. Abdel - Magid et al., Tetrahedron letters, 31, 5595 (1990), followed by the removal of the protection groups thereof, or by a method consisting of saturation or non-saturation bonds with a reducing agent, as the occasion may demand. The above aspartame derivative can be obtained by a usual peptide synthesis method, as discussed in Izumiya et al., Fundamentals and Experimentation in Peptide Synthesis, published by MARUZEN on January 20, 1985. The method for the synthesis of the compounds In the present invention it is, however, not limited to these methods. In place of the aforementioned 3-phenylpropionaldehyde derivative, the cinnamaldehyde derivative or the (2-phenylethyl) alkyl ketone derivative, acetal or ketal derivatives thereof, can, of course, be used as the aldehyde or ketone components at the time of the alkylation reductive As a result of sensory evaluation, the derivative, which is the compound, and the salt forms thereof, according to the present invention, have been found to have strong sweetening potency and sensory properties similar to those of sugar. For example, the sweetness of N- [N- [3- (3-hydroxy-4-methoxyphenyl) -3-methylbutyl] -L-a-aspartyl] -L-phenylalanine 1-methyl ester was approximately 70000 times that of the sugar, the sweetness of 1-methyl ester of N- [N- [3- (3-methyl-4-hydroxyphenyl) -3-methylbutyl] -L-aspartyl] -L-phenylalanine was about 70000 times that of the sugar, the sweetness of N- [N- [3- (3-hydroxy-4-methylphenyl) -3-methylbutyl] -L-aspartyl] -L-phenylalanine 1-methyl ester was about 60000 times that of of sugar, and the sweetness of N- [N- [(RS) -3- (3-hydroxy-4-methoxyphenyl) butyl] -L-aspartyl] -L-phenylalanine 1-methyl ester was about 50000 times that of the sugar. On the other hand, the half-life in a buffer of pH = 3.0 at 72.0 ° C of N- [N- [3- (3-methoxy-4-hydroxyphenyl) -3-methylbutyl] -La-aspartyl 1-methyl ester] -L-phenylalanine was 34.4 hours, which is substantially equivalent to the half-life of 1- N- [N- (3, 3-dimethylbutyl) -L-aspartyl] -L-phenylalanine methyl ester (31.4 hours under the same condition). Also, the half-life in a buffer with pH = 3.0 at 70.0 ° C aspartame, 1-methyl ester of N- [N- (3, 3-dimethylbutyl) -La-aspartyl] -L-phenylalanine, 1-methyl ester of N - [N- [3- (3-hydroxy-4-methoxyphenyl) -3-methylbutyl] -La-aspartyl] -L-phenylalanine and N-methyl-1-methyl ester N- [3- (4-hydroxyphenyl) -3-methylbutyl] -La-aspartyl] -L-phenylalanine, was measured, and was found to be 23.5, 38.3, 44.5 and 43.6 hours, respectively. Table 1 showed the structure of several synthesized N-alkylapartyl dipeptide ester derivatives, shown by the general formula (6), indicated below, and * í? - 26 results of sensory evaluation tests. As can be seen from the results of Table 1, the novel derivatives of the present invention are particularly excellent in sweetness (sweetening potency).

The structure of the N-alkylapartyl dipeptide ester derivative and potency Sweetness Table Power composition of No. R. R. R3 R6 R7 R? R11 R »R13 sweetness? 1 HH 0CH3 CH3 HH CH2CSHS H CH3 16000 2 H OH H CH3 HH CH2C6H5 H CH3 12000 3 H 0CH3 OH CH3 HH CH2C6HS H CH3 30000 4 H OH 0CH3 CH3 HH CH2C6HS H CH3 50000 5 H 0CH3 OH CH3 HH CH2CSH4 - p-OH H CH3 25000 6 H OH 0CH3 CH3 HH CH2C6H11 H CH3 40000 7 HH 0CH3 CH3 CH3 H CH2C6H5 H CH3 25000 ßHH OH CH3 CH3 H CH2C6HS H CH3 25000 9 H 0CH3 OH CH3 CH3 H CH2C6H5 H CH3 40000 10 H OH OCH3 CH3 CH3 H CH2C6HS H CH3 70000 11 H CH3 OH CHg HH CH2C6HS H CH, 50000 12 H OH? CH3 HH CH3 CH2C6HS H CH3 5000 13 OH H H CH 3 CH 3 H CH 2 C 6 H 5 H CH 3 8000 14 OH H 0 CH 3 CH 3 CH 3 H CH 2 C 6 HS H CH 3 20000 15 OH H CH3 CH3 CH3 H CH2CßHs H CH3 25000 16 H OCH .0 CH3 CH3 H CH2C6H5 H CH3 30000 17 H CH3 CH3 CH3 CH3 CH3 CH6C6H5 H CH3 300 H 18 CH3 OH CH3 CH3 CH2C6H5 H CH3 70000 19 H OH CH3 CH3 CH3 H CH2C6HS H CH3 60000 20 H 0CH3 OH CH2CH2CH2CH2 H CH2C6H5 H CH3 30000 21 H OH 0CH3 CH3 CH3 H CH2C6H5 H CH2CH3 15000 22 H OH 0CH3 CH3 CH3 H CH2CSH6 CH3 CH3 40000 23 H OH OH CH3 CH3 H CH2C6H5 H CH3 50000 *) values compared to sweetening power of an aqueous solution at 4% sucrose. Meanwhile, in the case where the derivatives of the present invention (compounds of the present invention including salt forms thereof) are used as a sweetening agent, it is of course possible to use other sweetening agents in combination. If the derivatives of the present invention are used as sweetening agents, it is of course possible to use a carrier and / or bulky agent, for example, a bulky carrier or agent hitherto known and used. The derivatives of the present invention can be used as a sweetening agent or a component thereof. In addition, the derivatives of the present invention can be used for products, such as foods or similar products, in need of sweet taste, such as confectionery chewing gum, sanitary products, toiletries, cosmetics, pharmaceuticals and various veterinary products for animals different from those for humans. In addition, the derivatives of the present invention can be used as a product form to be given or endowed with a sweet taste and a sweet taste imparting method for products (foods or similar products) in need of a sweet taste. As for the method of using the derivatives of the present invention, any suitable conventional or well-known methods can be followed. PREFERRED EMBODIMENTS FOR CARRYING OUT THE INVENTION The present invention will be explained in detail with reference to the Examples, which, however, are merely illustrative and are not intended to limit the present invention. The NMR spectrum and the MS spectrum were measured using Varian Gemini 300 (300 MH) and Thermo Quest TSW700, 5 respectively. (Example 1) Synthesis of N- [N- [3- (3-hydroxy-4-methoxyphenyl) -3-methylbutyl] -L-α-aspartyl] -L-phenylalanine 1-methyl ester (Table 1, compound number 10) 703 mg (1.45 mmoles) of Nt-butoxycarbonyl-β-O-benzyl-α-L-aspartyl-L-phenylalanine, 10 ml of 4N-HCl / dioxane solution were stirred and stirred at room temperature for one hour. The reaction solution was concentrated under reduced pressure. To the residue was added 50 ml of a 5% aqueous solution of sodium hydrogencarbonate and the extraction was made twice with 50 ml of ethyl acetate. An organic layer was washed with saturated saline water and dried over anhydrous magnesium sulfate. The magnesium sulfate was filtered and the liquid filtrate was concentrated under reduced pressure to yield 557 mg (1.45 mmol) of β-O-benzyl-α-aspartyl-L-phenylalanine methyl ester as a viscous oily substance. 557 mg (1.45 moles) of the methyl ester of β-O-benzyl-a-L-aspartyl-L-phenylalanine was dissolved in 15 ml of tetrahydrofuran (THF) to produce a solution which - * '- * 30 moles) of 3- (3-benC ^ oxy-4-methoxyphenyl) -3-methylbutylaldehyde 0.083 ml (1.45 mmol) of acetic acid and 462 mg (2.18 mmol) of NaB (OAc) 3H and stirred for one hour at 0 ° C and overnight at room temperature. To the reaction solution was added 50 ml of a saturated aqueous solution of sodium hydrogencarbonate and the extraction was made twice with 50 ml of ethyl acetate. An organic layer was washed with saturated saline water and dried over anhydrous magnesium sulfate. Magnesium sulfate was filtered and the filtrate The liquid was concentrated under reduced pressure. The residue was purified with preparative thin layer chromatography (PLTC) to yield 832 mg (1.25 mmoles) of N- [N- [3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutyl] -β-1-methyl ester. -O-benzyl-La-aspartyl] -L-phenylalanine as a viscous oily substance. The 1-methyl ester of 832 mg N- [N- [3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutyl] -β-O-benzyl-La-aspartyl] -L-phenylalanine was dissolved ( 1.25 mmoles) in a mixed solvent of 25 ml of methanol and 2 ml of water, and 350 mg of 10% palladium carbon (containing 50% of water) were added to it. The resulting mixture was reduced to room temperature for three hours under a hydrogen atmosphere. The catalyst was filtered and the filtrate was concentrated under reduced pressure. The residue was purified with PTLC to remove an adsorbed odor to produce 400 mg (0.82 mmol) of the N- [N- [3- (3-hydroxy-4-methoxyphenyl) -3-methylbutyl] -l-methyl ester. aspartyl] -L-phenylalanine as a solid substance. XHMMR (DMSO-d6) d: 1.14 (s, 6H9, 1.54-1.68 (m, 2H), 2.04-2.22 (m, 3H), 2.24-2.34 (dd, 1H), 2.84-2.94 (dd, 1H), 3.00-3.08 (dd, 1H), 3.31-3.36 (m, 1H), 3.59 (s, 3H), 3.71 (s, 3H), 4.46-4.55 (m, 1H), 6.60-6.65 (dd, 1H) 6.73 (s, 1H), 6.80 (d, 1H), 7.10-7.28 (m, 5H), 8.45 (d, 1H), 8.75 (brs, 1H) ESI (Electroaspersion Ionization) - MS 487.3 (MH +) Sweetness ( sweetening power), 70000 times the sweetness of the sugar (Example 2) Synthesis of the N- [N- [3- (4-methoxyphenyl) -3-methylbutyl] -L-aspartyl] -L-phenylalanine 1-methyl ester (Table 1, compound number 7) The N- [N- [3- (4-methoxyphenyl) -3-methylbutyl] -L-α-aspartyl] -L-phenylalanine 1-methyl ester was obtained as a solid substance, with a total yield of 72.2%, in the same manner as in Example 1, except that 3- (4-methoxyphenyl) -3-methylbutylaldehyde is used in place of 3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutylaldehyde XHMMR ( DMSO-de) d: 1.17 (s, 6H9, 1.62-1.72 (m, 2H), 2.04-2.20 (m, 3H), 2.24 - 2.34 (dd, 1H), 2.84-2.94 (dd, 1H), 2.95-3.07 (dd, 1H), 3.30-3.35 (m, 1H), 3.51 (s, 3H), 3.70 (s, 3H9, 4.46-4.54 (m, 1H), 6.83 (d, 2H), 7.14-7.28 (m, 7H), 8 43 (d, H). ESI-MS 471. 3 (MH +) Sweetness, 25,000 times the sweetness of sugar (Example 3) 5 Synthesis of 1 methyl ester of N- [N- [3- (4-hydroxyphenyl) -3-methylbutyl] -La-aspartyl] -L-phenylalanine (Table 1, compound number 8) N- [N- [3- (4-hydroxyphenyl) -3-methylbutyl] -La-aspartyl] -L-phenylalanine 1-methyl ester was obtained as a solid substance, with a total production of 64.5% in the same manner as in Example 1, except that 3- (4-benzylxyphenyl) -3-methylbutylaldehyde is used instead of 3-83-benzyloxy-4- methoxyphenyl) -3-methylbutylaldehyde. XHMMR (DMSO-de) d: 1.15 (s, 6H9, 1.58-1.72 (m, 2H), 15 2.04-2.20 (m, 3H), 2.24-2.34 (dd, 1H), 2.85-2.94 (dd, 1H) , 3.00-3.08 (dd, 1H), 3.30-3.36 (m, 1H9, 3.59 (s, 3H), 4.46- 4.55 (m, 1H), 6.67 (d, H), 7.07 (d, 2H), 7.10- 7.27 (m, 5H), 8.44 (d, 1H9, 9.15 (brs, 1H9) ESI-MS 457.3 (MH +) 20 Sweetness, 25,000 times the sweetness of sugar (Example 4) Synthesis of 1-methyl ester of N- [N- [ 3- (3-methoxy-4-hydroxyphenyl) -3-methylbutyl] -La-aspartyl] -L-phenylalanine (Table 1, compound number 9) 25 N- [N- [3-methoxy] 1-methyl ester was obtained -4- hydroxyphenyl) -3-methylbutyl] -L-aspartyl] -L-phenylalanine as a solid substance, with a total yield of 62.2% in the same manner as in Example 1, except that 3- (3-methoxy-4 is used -benz-loxyphenyl) -3-methylbutylaldehyde in place of 5- 3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutylaldehyde. : HMMR (DMSO-d6) 5: 1.17 (s, 6H), 1.63-1.72 (m, 2H), 2.08-2.22 (m, 3H9 2.25-2.33 (dd, 1H), 2.86-2.94 (dd, 1H), 3.00-3.08 (dd, 1H), 3.33-3.38 (m, 1H), 3.59 (s, 3H9, 3.75 (s, 3H), 3.47-3.55 (m, H), 6.67 (s, 2H), 6.81 (s) , 1H), 7.14-7.27 (m, 5H), 8.46 (d, 1H), 8.70 (brs, 1H). ESI-MS 487.3 (MH +) Sweetness, 40000 times the sweetness of sugar (Example 5) Synthesis of N- [N- [3- (3-hydroxy-4- 15-methoxyphenyl) -3-methylbutyl] -methyl ester] -La -aspartyl] -L- (α-methyl) phenylalanine (Table 1, compound number 22) A N- [N- [3- (3-hydroxy-4-methoxyphenyl) -3- 1-methyl ester was obtained as a solid substance. methylbutyl] -La-aspartyl] -L- (a-methyl) phenylalanine, with a total yield of 77.2%, in the same manner as in Example 1, except that methyl ester of N-butoxycarbonyl-β-O is used -benzyl- aL-aspartyl-L- (a-methyl) -phenylalanine in place of the N-t-butoxycarbonyl-β-O-benzyl-α-L-aspartyl-L-phenylalanine methyl ester. XHMMR (DMSO-de) d: 1.18 (s, 6H), 1.22 (s, 3H), 1.66- 3. 36-3.42 (m, 1H), 3.49 (s, 3H), 3.72 (s, 3H), 6.67 (dd, 1H), 6.74 (d, 1H), 6.80 (d, 1H), 7.02-7.06 (m, 2H), 7.20-7.30 (m, 3H), 8.29 (brs, 1H), 8.75 (brs, 1H). ESI-MS 501.3 (MH +) Sweetness, 40000 times the sweetness of sugar (Example 6) Synthesis of 1-methyl ester of N- [N- [3- (2-hydroxyphenyl) -3-methylbutyl] -La-aspartyl] - L-phenylalanine (Table 1, compound number 13) N- [N- [3- (2-hydroxyphenyl) -3-methylbutyl) -L-α-aspartyl] -L-phenylalanine 1-methyl ester was obtained as a solid substance, with a total yield of 64.5% in the same manner as in Example 1, except that 3- (2-benzyloxyphenyl) -3-methylbutylaldehyde is used in place of 3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutylaldehyde . * HMMR (DMSO-de) d: 1.26 (s, 6H), 1.84-2.30 (m, 6H), 2.88 (dd, 1H), 3.02 (dd, 1H), 3.32-3.38 (m, 1H), 3.59 ( s 3H), 4.45-4.54 (m, 1H), 6.68-6.78 (m, 3H), 6.96-7.06 (m, 2H), 7.12-7.30 (m, 5H), 8.50 (d, H), 9.30 (brs , 1 HOUR) . ESI-MS 457.4 (MH +) Sweetness, 8000 times the sweetness of sugar (Example 7) Synthesis of N- [N- [3- (2-hydroxy-4-methoxyphenyl) -3-methylbutyl] -l-methyl ester aspartyl] -L-phenylalanine (Table 1, compound number 14) The 1-methyl ester of N- [N- [3- (2-hydroxy-4-methoxyphenyl) -3-methylbutyl] -La-aspartyl] - was obtained L-phenylalanine as a solid substance, with a total yield of 44.1% in the same manner as in Example 1, except that 3- (2-benzyloxy-4-methoxyphenyl) -3-methylbutylaldehyde is used instead of 3- ( 3-benzyloxy-4-mtoxyphenyl) -3-methylbutylaldehyde. XHMMR (DMSO-de) d: 1.22 (s 6H), 1.82-2.20 (m, 5H), 2.26 (dd, 1H), 2.88 (dd, 1H), 3.01 (dd, 1H), 3.34-3.40 (m, 1H), 3.59 (s, 3H), 3.64 (s, 3H), 4.46-4.53 (m, 1H), 6.28 (dd, 1H), 6.36 (d, 1H), 6.92 (d, 1H), 7.14-7.26 (m, 5H), 8.52 (d, 1H), 9.40 (brs, 1H). ESI-MS 487-3 (MH +) Sweetness, 20000 times the sweetness of sugar (Example 8) Synthesis of N- [N- [3- (2-hydroxy-4-methylphenyl) -3-methylbutyl] -methyl ester] - La-aspartyl] -L-phenylalanine (Table 1, compound number 15) The 1-methyl ester of N- [N- [3- (2-hydroxy-4-methylphenyl) -3-methylbutyl] -La-aspartyl was obtained ] -L-phenylalanine as a solid substance, with a total yield of 45.1%, in the same manner as in Example 1, except that 3- (2-bncyloxy-4-methylphenyl) -3-methylbutylaldehyde is used instead of 3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutylaldehyde. XHMMR (DMSO-de) d: 1.23 (s, 6H), 1.82-2.20 (m, 5H), 2. 14 (s, 3H), 2.25 (dd, 1H), 2.88 (dd, 1H), 3.01 (dd, 1H), 3.33-3.39 (m, 1H), 3.58 (s, 3H), 4.46-4.54 (m, 1H), 6.51 (d, 1H), 6.87 (s, 1H), 6.90 (d 1H), 7.10-7.23 (m, 5H), 8.51 (d, 1H), 9.20 (brs, 1H). ESI-MS 471.2 (MH +) Sweetness, 25,000 times the sweetness of sugar (Example 9) Synthesis of N- [N- [3- (3,4-methylenedioxyphenyl) -3-methylbutyl] -La-aspartyl 1-methyl ester] -L-phenylalanine (Table 1, compound number 16) The 1-methyl ester of N- [N- [3- (3, 4-methylenedioxyphenyl) -3-methylbutyl] -La-aspartyl] -L-phenylalanine was obtained as a solid substance, with a total yield of 69.7% in the same manner as in Example 1, except that 3- (3, 4-methylend? oxyphenyl? -3-met? lbut? laldehyde is used instead of 3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutylaldehyde XHMMR (DMSO-de) d: 1.16 (s, 6H), 1.60-170 (, 2H), 2.05-2.20 (m, 3H), 2.27 ( dd, 1H), 2.89 (dd, 1H), 3.03 (dd, 1H), 3.31-3.35 (m, 1H), 3.59 (s 3H), 4.46-4.54 (m, 1H), 5.94 (s, 2H), 6.72 (dd, 1H), 6.79 (d, 1H), 6.88 (d, 1H), 7.15-7.28 (m, 5H), 8.44 (d, 1H) ESI-MS 485.4 (MH +) Sweetness, 30000 times the sweetness of sugar (Example 10) Synthesis of 1-methyl ester of N- [N- [3- (3-methyl-4-methoxy) xyphenyl) -3-methylbutyl] -L-spartyl] -L-phenylalanine (Table 1, compound number 17) The N-methyl-1-methyl ester of N- [3- (3- (3-methyl-4-methoxyphenyl) - 3-methylbutyl] -La-aspartyl] -L-phenylalanine as a solid substance, with a total yield of 66.0 & in the same manner as in Example 1, except that 3- 83-methyl-4-methoxyphenyl) -3-methylbutylaldehyde is used in place of 3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutylaldehyde. XHMMR (DMSO-de) d: 1.16 (s), 6H), 1.63-1.72 (m, 2H), 2.13 (s, 3H), 2.08-2.20 (m, 3H), 2.25-2.32 (dd 1H) 2.85-2.95 (dd, 1H) 3.00-3.06 (dd, 1H), 2.25-232 (dd, 1H), 2.85-2.95 (dd, 1H), 3.00-3.06 (dd, 1H) 3.31-3.36 (m, 1H), 3.59 (s, 3H), 3.73 (s, 3H) ), 4.47-4.55 (m, 1H), 6.79-6.82 (m, 1H), 7.03-7.06 (m, 2H), 7.15-7.27 (m, 5H), 8.44-8.47 (d, 1H). ESI-MS 485.5 (MH +) Sweetness, 30000 times the sweetness of sugar (Example 11) Synthesis of N- [N- [3- (3-methyl-4-hydroxyphenyl) -3-methylbutyl 1-methyl ester] -La -aspartyl] -L-phenylalanine (Table 1, compound number 18) 1-methyl ester of N- [N- [3- (3-methyl-4-hydroxyphenyl] -3-methylbutyl] -La-aspartyl was obtained] -L-phenylalanine as a solid substance, with a total yield of 63.2%, in the same manner as in Example 1, except that 3- (3-methyl-4-benzyloxyphenyl) -3-methylbutylaldehyde is used instead of. 3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutylaldehyde. XHMMR (DMSO-d6) d: 1.14 (s, 6H), 1.59-1.68 (m, 2H), 2. 09 (s, 3H), 2.08-2.18 (, 3H), 2.25 (dd, 1H), 2.90 (dd, 1H), 3. 02 (dd, 1H), 3.30-3.36 (m, H), 3.59 (s, 3H) 4.46-4.54 (m, 1H) 6.68 (d, 1H) 6.88 (dd, 1H), 6.96 (s, 1H), 6.14-6.73 (m, 5H) 8.46 (d, 1H), 9.01 (brs, 1H). ESI-MS 471.4 (MH +) Sweetness 70000 times the sweetness of sugar (Example 12) Synthesis of N- [N- [2- [1- (3-methoxy-4-hydroxyphenyl) cyclopentyl] ethyl] 1-methyl ester-La -aspartyl] -L-phenylalanine (Table 1, compound number 20) The N-methyl-1- [N- [2- [1- (3-methoxy-4-hydroxy-phenyl) -cyclopentyl] -ethyl] -1-methyl ester was obtained -aspartyl] -L-phenylalanine as a solid substance, with a total yield of 68.4% in the same manner as in Example 1, except that 2- [1- (3-methoxy-4-hydroxy-phenyl) -cyclopentyl] -acetaldehyde was used instead of 3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutylaldehyde. XHMMR (DMSO-de) d: 1.48-1.82 (m, 10H9 2.00-2.16 (m, 3H), 2.24 (dd, 1H), 2.90 (dd 1H), 3.01 (dd, 1H) 3.30-3.40 (m, 1H), 3.59 (s, 3H) 3.74 (s, 3H), 4.45-4.53 (m, 1H), 6.59 (dd, 1H), 6.65 (d 1H), 6.75 (dd, 1H), 7.14-7.28 (, 5H), 8.44 (d, 1H), 8.70 (brs, 1H). ESI-MS 513.4 (MH +) Sweetness, 30000 times the sweetness of sugar (Example 13) Synthesis of N- [N- [3- (3-hydroxy-4-methoxyphenyl) -3-methylbutyl] 1-ethylester] -aspartyl] -L-phenylalanine (Table 1, compound number 21) N- [N- [3- (3-hydroxy-4-methoxyphenyl) -3-methylbutyl] -La-aspartyl] - 1-ethyl ester was obtained L-phenylalanine as a solid substance, with a total yield of 56.1% in the same manner as in Example 1, except that ethyl ester of Nt-butoxycarbonyl-β-O-benzyl-α-L-aspartyl-L-phenylalanine is used in Instead of the N-butoxycarbonyl-β-O-benzyl-α-L-aspartyl-L-phenylalanine methyl ester. XHMMR (DMSO-de) d: 1.09 1.13 (m, 9H), 1.58-1.67 (m, 2H), 2.08-2.37 (m, 4H), 2.86-2.93 (dd, 1H), 2.99-3.06 (dd, 1H ) 3.32-3.37 (m, 1H), 3.71 (s, 3H), 4.00-4.07 (m, 2H) 4.44- 4.51 (m, 1H), 6.62-6.65 (d, 1H), 6.74-6.81 (m, 2H) ), 7.15-7.27 (m, 5H9, 8.46 (d, 1H), 8.78 (brs, 1H) ESI-MS 501.3 (MH +) Sweetness, 15,000 times the sugar sweetness (Example 14) Synthesis of the 1-methyl ester of the N- [N- [(RS) -3- (3-methoxy-4-hydroxyphenyl) -butyl] -La-aspartyl] -L-phenylalanine (Table 1, compound number 3) Obtained in the same manner as in Example 1, 419 mg (1.09 mmol) of the β-O-benzyl-α-L-aspartyl-L-phenylalanine methyl ester was dissolved in 10 ml of THF and the resulting solution was kept at 0 ° C. To this solution was added 308 mg ( 1.09 mmoles) of 3- (3-methoxy-4-benzyloxyphenyl) -2-butenal, 0.062 ml (1.09 mmoles) of acetic acid and 345mg (1.63 mmoles) of NaB (OAc) 3H and the resulting mixture was stirred at 0 °. C for one hour and also stirred during the night at environmental perature. To the reaction solution was added 30 ml of a saturated aqueous solution of sodium hydrogencarbonate and the extractions were carried out twice with 30 ml of ethyl acetate. An organic layer was washed with saturated saline water and dried over anhydrous magnesium sulfate. After filtering the magnesium sulfate, the liquid filtrate was concentrated under reduced pressure. The residue was purified with preparative thin layer chromatography (PTLC) to obtain 534mg (0.82 mmoles) of N- [N- [3- (3-methoxy-4-benzyloxyphenyl) -2-butenyl] -β- 1-methyl ester. O-benzyl-La-aspartyl] -L-phenylalanine as a viscous oily substance. 534 mg (0.82 mmol) of the N- [N- [3- (3-methoxy-4-benzyloxyphenyl-2-butenyl-β-O-benzyl-La-aspartyl] -L-phenylalanine-1-methyl ester were dissolved in a mixed solvent of 20 ml of methanol and 1 ml of water, 200 mg of 10% palladium carbon (containing 50% water) was added to the resulting mixture.The resulting mixture was reduced to room temperature for three hours in a Hydrogen atmosphere The catalyst was filtered and the resulting filtrate was concentrated under reduced pressure. The residue was purified with PTLC to remove an adsorbed odor to obtain 269 mg (0.57 mmol) of N- [N- [(RS) -3- (3-methoxy-4-hydroxyphenyl) butyl] -1-methyl ester. aspartyl] -L-phenylalanine as a solid substance. XHMMR (DMSO-de) d: 1.10 (2d, 3H), 1.50-1.60 (m, 2H) 2.10-2.40 (m, 4H), 2.55-2.65 (m, 1H), 2.85-2.95 (m, 1H), 3.03-3.09 (dd, 1H) 3.34-3.40 (m, 1H), 3.60 (s, 1.5H), 3.61 (s, 1.5H), 3.74 (s, 1.5H9 3.75 (s, 1.5H), 4.50-4.60 (m, 1H), 6.55 (d, H ), 6.67 (d, 1H), 6.72 (s, 1H), 7.15-7.30 (m, 5H), 8.50 (brd, 1H), 8.70 / brs, 1H). ESI-MS 473.3 (MH +) Sweetness, 30000 times the sugar sweetness (Example 15) Synthesis of the N- [N- [(RS) -3- (4-methoxyphenyl) butyl] -La-aspartyl 1-methyl ester] -L-phenylalanine (Table 1, compound number 1) The 1-methyl ester of N- [N- [(RS = -3- (4-methoxyphenyl) butyl] -La-aspartyl] -L-phenylalanine was obtained as a solid substance with a total yield of 37.3% in the same manner as in Example 14, except that 3- (4-methoxyphenyl) -2-butenal was used instead of 3- (3-methoxy-4-benzyloxyphenyl) -2-butenal XHMMR (DMSO-de) d: 1.09 (d, 1.5H), 1.11 (d, 1.5H), 1.54 (m, 2H), 2.17-2.23 (, 3H), 2.28-2.38 (m 1H ), 2.64 (m, • * $ £ "$ 42 1H), 2.85-2.95 (m, 1H), 3.02-3.10 (dd, lH), 3.60 (s, 1.5H), 3.61 (s, 1.5H), 3.70 (s, 1H), 4.54 (m, 1H) , 6.83 (d, 2H), 7.07 (d, 2H), 7.18-7.28 (m, 5H). ESI-MS 457.3 (MH +) 5 Sweetness, 16,000 times the sweetness of sugar (Example 16) Synthesis of 1 N- [N- [(RS) -3- (3-hydroxyphenyl) butyl] -La-aspartyl] - methyl ester - L-phenylalanine (Table 1, compound number 2) The 1-methyl ester of N- [N- [(RS) -3- (3-hydroxyphenyl) butyl] -La-aspartyl] -L-phenylalanine was obtained as a solid substance with a total yield of 31.1% in the same manner as in Example 14, except that 3- (3-benzyloxyphenyl) -2-butenal is used in place of 3- (3-methoxy-4-15-benzyloxyphenyl) - 2-butenal XHMMR (DMSO-de) d: 1.09 (m, 3H), 1.55 (m, 2H), 2.10-2.24 (m, 3H9, 2.26-2.34 (dd, 1H), 2.58 (m, 1H), 2.85-2.98 ( m, 1H), 3.01-3.10 (dd 1H), 3.60 (s, 1.5H), 3.61 (s, 1.5H), 4.53 (m, 1H), 6.55-6.62 (m, 3H), 7.05 (t 1H), 7.16-7.30 (m, 5H) 8.47 (m, 1H), 8.75 (brs, 1H). ESI-MS 443.2 (MH +) Sweetness, 12,000 times the sweetness of sugar (Example 17) Synthesis of N- [N- [(RS) -3- (3-hydroxy-4-methoxyphenyl) butyl-1-methyl ester -aspartyl] -L-phenylalanine (Table 1, compound number 4) N- [N- [(RS) -3- (3-hydroxy-4-methoxyphenyl) butyl] -La-aspartyl 1-methyl ester was obtained] -L-phenylalanine as a solid substance with a total yield of 38.8% 5 in the same manner as in Example 14, except that 3- (3-benzyloxy-4-methoxyphenyl) -2-butenal is used instead of 3- (3-methoxy-4-benzyloxyphenyl) -2-butenal. XHMMR (DMSO-de) d: 1.08 (m, 3H), 1.53 (m, 2H), 2.13-2.21 (m, 3H) 2.28 (dd, 1H), 2.56 (m, 1H), 2.86-3.00 (m, 1H), 10 3.02-3.12 (dd, 1H), 3.29-340 (m, 1H), 3.60 (s, 1.5H9, 3.61 (s, 1.5H), 3.71 (s, 3H9, 4.53 (m, 1H), 6.53 (d, 1H), 6.60 (d, 1H), 6.79 (d, 1H), 7.15-7.26 (m, 5H), 8.46 (m, 1H), 8.75 (brs, 1H), ESI-MS 473.3 (MH + ) 15 Sweetness, 50000 times the sweetness of sugar (Example 18) Synthesis of N- [N- [3- ((RS) -3-hydroxy-4-methoxyphenyl) -butyl] -L-aspartyl 1-methyl ester] -3-cyclohexyl-L-alanine (Table 1, compound number 6) 20 The 1-methyl ester of N- [N- [(RS) -3- (3-hydroxy-4-methoxyphenyl) butyl] -La was obtained -aspartyl] -3-cyclohexyl-L-alanine as a solid substance with a total yield of 41.7% in the same manner as in Example 14, except that methyl ester of Nt-butoxycarbonyl-β-O-benzyl-a is used - 25 L-aspartyl-3-cyclohexyl-L-alanine instead of the methyl ester of "5 < w > 44 Nt-butoxycarbonyl-β-O-benzyl-aL-aspartl-1-L-enylalanine and also except that 3- (3-benzyloxy-4-methoxyphenyl) -2-butenal is used instead of 3- (3-methoxy-4-) benzyloxyphenyl) -2- butenal. 5 XHMMR (DMSO-de) d: 0.75-1.34 (m, 5H), 1.11 (d, 3H), 1.50-1.70 (m, 10H), 2.18-2.28 (m, 2H), 2.35-2.45 (m, 2H) ), 2.58-2.65 (m, 1H), 3.27-3.36 (m, 1H), 3.60 (m, 3H), 3.71 (s, 3H), 4.35 (m, 1H), 6.53-6.60 (m, 1H), 6.61 (d 1H), 6.79 (d, 1H9, 8.44 (m, 1H), 8.80 (brs, 1H) .10 ESI-MS 479.4 (MH +) Sweetness, 40000 times the sweetness of sugar (Example 19) Synthesis of 1- N- [N- [(RS) -3- (3-methoxy-4-hydroxyphenyl) butyl] -L-aspartyl] -L-tyrosine methyl ester (Table 1, 15 compound number 5) The 1-methyl ester was obtained of N- [N- [(RS) -3- (3-methoxy-4-hydroxyphenyl) -butyl] -La-aspartyl] -L-tyrosine as a solid substance with a total yield of 37.5% in the same manner as in Example 14, except that N-methyl-butoxycarbonyl-β-benzyl-α-L-aspartyl-L-tyrosine methyl ester is used in place of N-t-butoxycarbonyl-β-O-benzyl-α-L-aspartyl-L methyl ester phenylalanine XHMMR (DMSO-de) d: 1.10 (d, 3H), 1.55 (m, 2H), 2.16- 2.41 (m, 4H9, 2.58 (m, 1H) , 2.70-2.82 (m, 1H), 2.85-2.95 (dd, 1H), 3.58 (s, 3H), 3.78 (s, 3H), 4.43 (m, 1H), 6.53-6.75 (m, 5H9, 6.96 (d, 2H), 8.49 (brd, 1H), 8.75 (brs, 1H), 9.80 (brs, 1H) ESI-MS 489.3 (MH +) Sweetness, 25,000 times the sweetness of sugar (Example 20) Synthesis of N- [N- [(RS) -3- (3-methyl-4-hydroxyphenyl) butyl] -La-aspartyl] -L-fenlalanine 1-methyl ester (Table 1, compound number 11) The N- [N- [(RS) -3- (3-methyl-4-hydroxyphenyl) butyl] -L-α-aspartyl] -L-phenylalanine 1-methyl ester was obtained as a solid substance with a total yield of 19.7% in the same manner as in Example 14, except that 3- (3-methyl-4-betycyloxyphenyl) -2-butenal is used instead of 3- (3-methoxy-4-benzyloxyphenyl) - 2-butenal XHMMR (DMSO-de) d: 1.06-1.09 (m, 3H), 1.49-1.54 (m, 2H), 2.08 (m, 3H), 2.11-2.20 (m, 3H), 2.17-2.33 (m, 1H) , 2.85-2.95 (m, 2H), 3.05-3.09 (m, 1H), 3.33-3.37 (m, 1H), 3.61 (s, 3H) 4.50-4.55 (m, 1H), 6.65 (m, 1H), 6.76 (m, 1H), 6.84 (s, 1H9, 7.16-7.28 (m, 5H), 8.47-8.50 (m, 1H), 9.02 (brs, 1H) ESI-MS 457.2 (MH +) Sweetness, 50000 times the sugar sweetness (Example 21) Synthesis of N- [N- [3- (3-hydroxy-4-methoxyphenyl) - (RS) -2-methylpropyl] -La-aspartyl] -L-phenylalanine 1-methyl ester (Table 1, compound number 12) The 1-methyl ester of N- [N- [3- (3-hydroxy-4-methoxyphenyl) - (RS) -2-methylpropyl] -La-aspartyl] -L- was obtained phenylalanine as a solid substance with a total yield of 45.6% in the same manner as in Example 14, except that 3- (3-benzyloxy-4-methoxyphenyl) -2-methyl-2-propene is used instead of 3- (3-methoxy-4-benzyloxyphenyl) -2-butenal. * HMMR (DMSO-de) d: 0.68-0.85 (m, 3H9, 1.65-1.82 (m, 1H), 2.08- 2.37 (m, 2H), 2.27-2.30 (d, 4H), 2.94-3.10 (m, 2H), 3.43-3.45 (m, 1H), 3.62 (s, 3H), 3.72 (s, 3H), 4.48-4.59 (m, 1H), 6.49-6.59 (m, 2H), 6.77-6.80 (m, 1H), 7.20-7.29 (m, 5H), 8.57-8.58 (m, 1H), 8.92 (brs, 1H) ESI-MS 473.4 (MH +) Sweetness, 5000 times the sweetness of sugar (Example 22) Synthesis of 1 N- [N- [3- (3-hydroxy-4-methylphenyl) -3-methylbutyl] -L-aspartyl] -L-phenylalanine methyl ester (Table 1, compound number 19) was added 274 mg (0.97 mmol) of 3 - [(3-benzyloxy-4-methyl) phenyl] -3-methylbutylaldehyde, 353 mg (1.2 mmol) of aspartame and 100 mg of carbon in 10% palladium (containing 50% water) to 7 ml of methanol and stirred at room temperature for four hours in an atmosphere of it was concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography (PTLC) to yield 299 mg (0.64 mmol, 65.5%) of N- [N- [3- (3-hydroxy-4-methylphenyl) -3-methylbutyl 1-methyl ester ] -La-aspartyl] -L-phenylalanine as a solid substance. XHMMR (DMSO-de) d: 1.14 (s, 6H), 1.58-1.70 (m, 2H), 2.05 (s, 3H), 2.07-2.42 (m, 4H), 2.89 (dd, 1H), 3.03 (dd) , 1H), 3.30-3.40 (m, 1H), 3.59 (s, 3H), 4.46-4.54 8m, 1H), 6.60 (d, 1H), 6.73 (s, 1H), 6.94 (d, 1H), 7.15 -7.30 (m, 5H), 8.46 (brs, 1H), 9.08 (brs, 1H). ESI-MS 471.3 (MH +) Sweetness, 60000 times the sweetness of sugar (Example 23) Synthesis of N- [N- [3- (3,4-dihydroxyphenyl) -3-methylbutyl] -La-aspartyl 1-methyl ester] -L-phenylalanine (Table 1, compound number 23) The N- [N- [3- (3, 4-dihydroxyphenyl) -3-methylbutyl] -L-α-aspartyl] -L-phenylalanine 1-methyl ester was obtained as a solid substance with a total yield of 76.5% in the same manner as in Example 1, except that 3- (3,4-dibenzyloxyphenyl) -3-methylbutylaldehyde is used in place of 3- (3-benzyloxy-4-methoxyphenyl) -3-methylbutylaldehyde. XHMMR (DMSO-de) d: 1.14 (s, 6H) 1.76-1.93 (m, 2H), 2.40-2.50 (m, 2H), 2.73-2.80 (m, 2H), 2.91 (dd, 1H), 3.06 ( dd, 1H), 3.59 (s 3H), 3.95-4.05 (m, 1H) 4.45-4.55 (m, 1H), 6. 52 (d, 1H), 6.64-6.70 (m, 2H), 6.94 (d, 1H), 7.15-7.30 (m, 5H), 8.73 (brs, 1H), 8.80 (brs, 1H), 90.9 (brs, 1 HOUR) . ESI-MS 473.3 (MH +) Sweetness, 50000 times the sweetness of sugar 5 Effect of the Invention The N-alkylsilicate dipeptide ester derivative according to the present invention is low in calories and exhibits a sweetening potency which is particularly superior, in comparison with conventional sweetening agents. In the present invention, a novel chemical substance having superior properties as a sweetening agent can be provided. The novel derivative can be used not only for a sweetening agent, but also for the production of sweetness to foods or similar products, such as drinks (drinks) and foods, which require sweet taste.

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Claims (28)

1. CLAIMS 1. A N-alkylapartyl dipeptide ester derivative, which includes its salt form, represented by the following general formula (1): wherein Ri, R2, R3, R4 and R5 are mutually independent and mean a substituent selected from the group consisting of a hydrogen atom, a hydroxyl group, an alkoxy group having from 1 to 3 carbon atoms, a group alkyl having from 1 to 3 carbon atoms and a hydroxyalkyloxy group having from two to three carbon atoms, or Ri and R2, or R2 and R3 are combined together and mean a methylenedioxy group. with the proviso that in the case that Ri and R2, or R2 and R3 combined together mean a methylenedioxy group, R4 and R5 and Ri or R3 which are not combined together with R2, are mutually independent and mean one of the aforementioned substituents previously designated by the symbol; where R6, R7, R8, R9 and Rio are reciprocally independent and signifying a substituent selected from the group consisting of a hydrogen atom and an alkyl group with 1 to 3 carbon atoms and optionally two substituents selected from Rβ, R7, Rs, R9 and Rio may be combined together herein and mean a alkylene group with 1 to 5 carbon atoms; with the proviso that, if any of the two optional substituents selected from Rβ, R7 R8, Rg and Rio combine together and mean an alkylene group having 1 to 5 carbon atoms, the substituents different from the two substituents selected are reciprocally independent and mean one of the previously defined substituents designated respectively by the symbol; wherein Ru means a substituent selected from the group consisting of a hydrogen atom, a benzyl group, a p-hydroxybenzyl group, a cyclohexylmethyl group, a phenyl group, a cyclohexyl group, a phenylethyl group and a cyclohexylethyl group, and Ri 2 means a substituent selected from the group consisting of a hydrogen atom and an alkyl group with 1 to 3 carbon atoms, and R 3 means a substituent selected from the group consisting of an alkyl group with 1 to 4 carbon atoms. provided that the derivatives in which R, R7, R8, Rg and Rio in their entirety mean a hydrogen atom at this same time, those in which Re means a methyl group, Rx, R2, R3, R4, R5 , R7, Rs, R9, Rio, and R12 mean a hydrogen atom at the same time and Rn 5 means a benzyl group or a p-hydroxybenzyl group at the same time, and those where R2 means a methoxy group, R3 means a group hydroxyl, Rio means a methyl group, Ri, R 4, R 5, R b, R 7, R s and R 9 signify a hydrogen atom at the same time, and Ru means a benzyl group 10 or a p-hydroxy group, are excluded.
2. 2. The derivative according to claim 1, characterized in that R3 signifies a methoxy group Ri, R2, R4, R5, R7, R8, Rg, Rio and R12 signify a hydrogen atom, R and R13 signify a methyl group and Rn means a group 15 benzyl.
3. 3. The derivative according to claim 1, characterized in that R2 means a hydroxyl group, Ri, R3, R4, R5, R7, R8, Rg, Rio and R12 signify a hydrogen atom, Rβ and R13 signify a methyl group, and Rn means 20 a benzyl group.
4. 4. The derivative according to claim 1, characterized in that R2 means a methoxy group, R3 signifies a hydroxyl group, Ri, R, R5, R7, R8, Rg, Rio and R12 signify a hydrogen atom, Re and R13 signify a group Methyl and R1X mean a benzyl group.
5. 5. The derivative according to claim 1, characterized in that R2 means a hydroxyl group, R3 signifies a methoxy group, Ri, R4, Rs, R7, Rs, R9, Rio and R12 signify a hydrogen atom, Re and R13 signify a group methyl and Rn means a benzyl group.
6. 6. The derivative according to claim 1, characterized in that R2 means a methoxy group, R3 signifies a hydroxy group, Ri, R4, R5, R7, R8, Rg, Rio and R12 signify a hydrogen atom, R6 and R13 signify a methyl group and Rn signifies a group p- hydroxybenzyl.
7. 7. The derivative according to claim 1, characterized in that R2 means a hydroxyl group, R3 signifies a methoxy group, Ri, R4, R5, R7, R8, Rg, Rio and R12 signify a hydrogen atom, Rβ and R13 signify a methyl group and Ru means a cyclohexylmethyl group.
8. 8. The derivative according to claim 1, characterized in that R3 means a methoxy group, Ri, R2, R4, R5, R8, Rg, Ro and R? 2 mean a hydrogen atom, R6, R7 and R13 mean a group methyl, and Rn means a benzyl group.
9. 9. The derivative according to claim 1, characterized in that R3 signifies a hydroxyl group, Ri, R2, R4, R5, R8, Rio and R12 signify a hydrogen atom, Rβ, R7 and Ri3 signify a methyl group, and Ru means a group
10. 10. The derivative according to claim 1, characterized in that R2 means a methoxy group, R3 signifies a hydroxyl group, Ri, R4, R5, R8, Rg, Rio and Ri2 signify a hydrogen atom, Rβ, R7 and R13 mean a methyl group, and Rn means a benzyl group.
11. 11. The derivative according to claim 1, characterized in that R2 means a hydroxyl group, R3 means a methoxy group, Ri, R4, Rs, R8, Rg, Rio and R12 means a hydrogen atom, Re, R7 and R13 means a methyl group, and Ru means a benzyl group.
12. 12. The derivative according to claim 1, characterized in that R2 means a methyl group, R3 signifies a hiroxyl group, Ri, R4, R5, R7, R8, Rg, Rio and R12 signify a hydrogen atom, R6 and R13 signify a methyl group, and Rn means a benzyl group.
13. 13. The derivative according to claim 1, characterized in that R2 means a hydroxyl group, R3 signifies a methoxy group, Ri, R4, R5, R6, R7, R9, Rio and R12 signify a hydrogen atom, R8 and R13 they mean a methyl group, and Ru means a benzyl group.
14. 14. The derivative according to claim 1, characterized in that Ri means a hydroxyl group, R2, R3, R4, R5, R8, R9, Rio and? 2 mean a hydrogen atom, R6, R7 and R13 mean a methyl group , and Ru means a benzyl group.
15. 15. The derivative according to claim 1, characterized in that Ri signifies a hydroxyl group, R3 signifies a methoxy group, R2, R4, Rs, Rs, 9, io and R12 signify a hydrogen atom, Rβ R and R13 signify a group methyl, and Rn means a benzyl group.
16. 16. The derivative according to claim 1, characterized in that Ri signifies a hydroxyl group, R3 signifies a methyl group, R2, R4, R5, Rs, R9, Rio and R? 2 signify a hydrogen atom, R?, R7 and R13 signifies a methyl group, and Rn signifies a benzyl group.
17. 17. The derivative according to claim 1, characterized in that R2 and R3 combine together and mean a methylenedioxy group, Ri R4, R5, R8, Rg, Rio and R12 signify a hydrogen atom, Rβ, R7 and R13 mean a methyl group, and Ru means a benzyl group.
18. 18. The derivative according to claim 1, characterized in that R2 means a methyl group, R3 signifies a methoxy group, Ri, R4, R5, R8, Rg, Rio and Ri2 signify a hydrogen atom, R, R7 and R13 mean a methyl group, and R means a benzyl group.
19. 19. The derivative according to claim 1, characterized in that R2 means a methyl group, R3 signifies a hydroxyl group, Ri, R4, R5, R8, Rg, io and R12 signify a hydrogen atom, R6, R7 and R13 signify a methyl group, and Ru means a benzyl group.
20. 20. The derivative according to claim 1, characterized in that R2 means a hydroxyl group, R3 signifies a methyl group, Ri, R4, R5, R8, Rg, Rio and R12 signify a hydrogen atom, Rβ, R. and Ri3 signify a methyl group, and R means a benzyl group.
21. 21. The derivative according to claim 1, characterized in that R2 means a methoxy group, R3 signifies a hydroxyl group, Ri, R4, R5, R8, R9, Rio and R12 signify a hydrogen atom, R6 and R7 are combined together and they mean a tetramethylene group, Ru means a benzyl group, and R13 means a methyl group.
22. 22. The derivative according to claim 1, characterized in that R2 means a hydroxyl group, R3 signifies a methoxy group, Ri, R4 R5, R8, R9, Rio and R12 signify a hydrogen atom, Rβ and R7 signify a methyl group , Rn means a benzyl group, and R13 means an ethyl group.
23. 23. The derivative according to claim 1, characterized in that R2 means a hydroxyl group, R3 signifies a methoxy group, Ri, R4, R5, R8, R9 and Rio signify a hydrogen atom, R6, R7, R12 and R13 mean a methyl group, and Rn means a benzyl group.
24. 24. The derivative according to claim 1, characterized in that R2 and R3 mean a hydrogen atom, R6, R7 and R13 signify a methyl group, and R11 signifies a benzyl group.
25. 25. The derivative according to any of claims 1 to 7 and 12, characterized in that if the substituent R6 and R7 differ from each other, the configuration of the carbon atom to which R is linked in the formula, is in the status of (R), (S) or (RS).
26. 26. The derivative according to claim 1 or 13, characterized in that if the substituent R8 and Rg differ from each other, the configuration of the carbon atom to which R8 is bound in the formula, is in the state of (R) , (S) or (RS).
27. 27. The derivative according to claim 1, characterized in that, if Rio means a substituent different from a hydrogen atom, the configuration of the carbon atom to which R10 is bound in the formula, is in the state of (R), (S) or (RS).
28. 28. A sweetening agent, or a sweetening food or the like product comprising the derivative according to claim 1, as an effective component, which optionally contains a bulky carrier or agent for the sweetening agents. The novel N-alkylapartyl dipeptide ester derivative, such as N- [N- [3- (3-hiroxy-4-methoxyphenyl) -3-methylbutyl] -L-aspartyl] -L-phenylalanine 1-methyl ester , including that in the salt form, which can be used as an excellent sweetening agent, is provided. The novel derivative is low in calories and moreover it is more particularly excellent in a sweetening potency as compared to conventional sweetening agents, and therefore allows the supply of a sweetening agent, food or the like product containing the derivative. I heard z < (oz