Process for producing .alpha.-aspartyl-phenylalanine ester

• US 4,730,076 A
• Filed: 12/16/1986
• Issued: 03/08/1988
• Est. Priority Date: 12/18/1985
• Status: Expired due to Fees

• Current Assignee: Nippon Kayaku Company Limited
• Original Assignee: Nippon Kayaku Company Limited
• Inventors: Aoki, Shigeru, Tsuda, Makoto, Yagiuchi, Hiroshi, Fujii, Tadashi, Mitsunobu, Akikazu
• Primary Examiner(s): Shippen, Michael L.
• Assistant Examiner(s): Gray, Bruce D.
• Application Number:
  US06/942,146
• Time in Patent Office: 448 Days
• Field of Search: 560/41, 530/801
• US Class Current: 560/41
• CPC Class Codes: C07K 5/0613 Aspartame

Abstract

The present invention relates to a process for producing α-aspartyl-phenylalanine ester represented by the general formula ##STR1## wherein R'"'"' represents an alkyl group having 1 to 4 carbon atoms, by reducing an N-protected-N-hydroxymethyl-α-aspartyl-phenylalanine ester represented by the general formula ##STR2## wherein R represents an organic mioety which can be substituted reductively by hydrogen, and R'"'"' is as defined above, with hydrogen gas or formic acid, in the presence of a reduction catalyst and an aromatic primary amine. According to the present invention, there can be obtained a high purity α-aspartyl-phenylalanine ester with a high yield.

Claims

1. A process for producing α

-aspartyl-phenylalanine ester represented by the general formula (I) ##STR10## wherein R'"'"' represents an alkyl group having 1 to 4 carbon atoms, which comprises reducing an N-protected-N-hydroxymethyl-α

-aspartyl-phenylalanine ester represented by the general formula (IV) ##STR11## wherein R represents an organic moiety which can be substituted by hydrogen reductively, and R'"'"' is as defined above, with hydrogen gas or formic acid in the presence of a reduction catalyst and an aromatic primary amine.

2. A process according to claim 1, wherein R represents an unsubstituted benzyloxycarbonyl group or a benzyloxycarbonyl group substituted by a halogen atom, a lower alkoxy group, a lower alkyl group or a nitro group, R'"'"' represents a methyl group, a reduction catalyst represents a palladium type catalyst, and an aromatic primary amine represents an aniline which may be substituted by a lower alkyl group, a halogen atom, a nitro group or a lower alkoxy group.

3. A process according to claim 2, wherein R represents unsubstituted benzyloxycarbonyl group.

4. A process according to claim 1, wherein an amount of reduction catalyst is 0.5 to 40% by weight of the compound represented by the general formula (IV).

5. A process according to claim 1, wherein an amount of reduction catalyst is 1 to 15% by weight of the compound represented by the general formula (IV), when hydrogen gas is used, and is 5 to 30% by weight, when formic acid is used.

6. A process according to claim 1, wherein the aromatic primary amine is aniline.

7. A process according to claim 1, wherein an amount of the aromatic primary amine is 0.1 to 3 equivalents of the compound represented by the general formula (IV).

8. A process according to claim 1, wherein an amount of formic acid is 1 to 10 times by mol the compound represented by the general formula (IV).

9. A process according to claim 1, wherein the amount of aromatic primary amine is 0.5 to 1.5 equivalents and the amount of formic acid is 1 to 3 times by mol to the compound represented by the general formula (IV).

10. A process for producing α

-aspartyl-phenylalanine lower alkyl ester which comprises reducing N-benzyloxycarbonyl-N-hydroxymethyl-α

-aspartyl-phenylalanine lower alkyl ester with hydrogen gas in a mixed solvent of water and a lower alcohol in the presence of palladium-carbon and aniline.

11. A process for producing α

-aspartyl-phenylalanine lower alkyl ester which comprises reducing N-benzyloxycarbonyl-N-hydroxymethyl-α

-aspartyl-phenylalanine lower alkyl ester with formic acid in a mixed solvent of water and a lower alcohol in the presence of palladium-carbon and aniline.