Ajinomoto Co., Ltd.

Shinji Fujita

Tadashi Takemoto

Kenichi Mori

Nao Funakoshi

Shigeru Kawahara

Kazutaka Nagashima

Satoji Takahashi

Toshihisa Kato

Eriko Ono

Yuuichi Aoki

Naoko Sugiyama

Mikiya Kano

A process for conveniently and efficiently producing a highly pure cinnamaldehyde derivative, for example, (2E)-(3-hydroxy-4-methoxy)cinnamaldehyde, which comprises reacting a benzaldehyde derivative, such as isovanillin and the like, with acetaldehyde in the presence of an alkali, in particular preferably, dropping acetaldehyde little by little thereto in an aqueous solution at a low temperature for the reaction thereof. The cinnamaldehyde derivative thus obtained is selectively reduced to produce 3-(3-hydroxy-4-substituted (with methoxy group or the like)phenyl)propionaldehyde. Further, through a reductive alkylation reaction of the compound thus produced with an aspartame, N-[N-[3-(3-hydroxy-4-substituted (with methoxy group or the like)phenyl)propyl]-L-aspartyl]-L-phenylalanine 1-methyl ester, which is useful as a sweetener having a high sweetening potency, can be industrially and efficiently produced. The processes therefor are also provided.

Process for producing cinnamaldehyde derivatives, use thereof and the like

A process for conveniently and efficiently producing a highly pure cinnamaldehyde derivative, for example, (2E)-(3-hydroxy-4-methoxy)cinnamaldehyde, which comprises reacting a benzaldehyde derivative, such as isovanillin and the like, with acetaldehyde in the presence of an alkali, in particular preferably, dropping acetaldehyde little by little thereto in an aqueous solution at a low temperature for the reaction thereof. The cinnamaldehyde derivative thus obtained is selectively reduced to produce 3-(3-hydroxy-4-substituted (with methoxy group or the like)phenyl) propionaldehyde. Further, through a reductive alkylation reaction of the compound thus produced with an aspartame, N-[N-[3-(3-hydroxy-4-substituted (with methoxy group or the like)phenyl) propyl]-L-&#x3b1;-aspartyl]-L-phenylalanine 1-methyl ester, which is useful as a sweetener having a high sweetening potency, can be industrially and efficiently produced. The processes therefor are also provided.

N-[N-[3-(2-hydroxy-substituted phenyl)propyl]-L-&#x3b1;-aspartyl]-L-phenylalanine 1-methyl ester derivatives, which are useful as sweeteners, may be conveniently produced by subjecting a 2-hydroxychroman derivative having various substituents on the benzene ring and aspartame to a reductive alkylation reaction. These compounds may be purified by subjecting such a derivative containing one or more impurities to a crystallization step to crystallize the same. Further, there are provided a process for producing dialkoxychroman derivatives useful as intermediates for the production of such aspartame derivatives in the above process, and novel dialkoxychroman derivatives thus produced, which are excellent as the production intermediate.

Process for producing aspartame derivatives, process for purifying aspartame derivatives, production intermediates, and process for producing production intermediates

A method is disclosed for the production of .alpha.-APM HCl by treating an F-.alpha.-AP derivative with a mixed solvent of methanol, hydrochloric acid and water, wherein the solubility of .alpha.-APM HCl is lowered to increase the separation yield thereof.

Method for the production of .alpha.-L-aspartyl-L-phenylalanine methyl

A method is disclosed for the production of .alpha.-APM.HCl by treating an F-.alpha.-AP derivative with a mixed solvent of methanol, hydrochloric acid and water, wherein the solubility of .alpha.-APM.HCl is lowered to increase the separation yield thereof.

This invention is directed to provide a method for obtaining .alpha.-L-aspartyl-L-phenylalanine selectively in high yields. Diffusion dialysis with an ion exchange membrane is used to decrease hydrochloric acid concentration of a mixed solution containing hydrochloric acid and one or more of four .alpha.-L-aspartyl-L-phenylalanine derivatives, i.e., .alpha.-L-aspartyl-L-phenylalanine methyl ester, .alpha.-L-aspartyl-L-phenylalanine, .alpha.-L-aspartyl-L-phenylalanine-.beta.-methyl ester and .alpha.-L-aspartyl-L-phenylalanine dimethyl ester. The resultant solution is concentrated, to which a base is added for neutralization. Subsequently, .alpha.-L-aspartyl-L-phenylalanine is crystallized and isolated.

Method for preparing .alpha.-L-aspartyl-L-phenylalanine

A method of crystallizing phenylalanine in the form of .alpha.-crystals at a temperature below .alpha..fwdarw..beta. transition temperature comprises:

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Kawasaki, Japan

Shinji Fujita