Ajinomoto Co., Ltd.

Yasuo Ariyoshi

Tadashi Takemoto

Naohiko Yasuda

Koji Toi

Fusayoshi Kakizaki

Ichiro Noda

A process for producing .alpha.-L-aspartyl-L-phenylalanine methyl ester or its hydrochloride which comprises contacting N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester with a mixture of methanol and a highly concentrated hydrochloric acid at a temperature of between 0.degree. and 40.degree. C., whereby the amino-protecting formyl group is removed and .alpha.-L-aspartyl-L-phenylalanine methyl ester crystalizes, and isolating the hydrochloride crystals, and, if desired, converting the hydrochloride to free .alpha.-L-aspartyl-L-phenylalanine methyl ester, is disclosed along with variations thereof. The process is commerically advantageous in that it utilizes inexpensive materials while minimizing hydrolysis of the peptide bond.

Process for producing .alpha.-L-aspartyl-L-phenylalanine methyl ester

The masking N-formyl group of an N-formyl-amino acid ester or an N-formyl-peptide ester having a free carboxyl group is removed without major side reactions when the ester is contacted with a strong acid in a mixture of water and a specific organic solvent such as methyl ethyl ketone or acetonitrile. This method is specifically applicable to the production of L-aspartyl amino acid lower alkyl esters which are known as low calorie sweeteners.

Method of removing formyl groups from N-formyl-amino acid and

The masking N-formyl group of an N-formyl-amino acid ester or N-formyl-peptide ester is removed without major side reactions when the ester is reacted in an inert liquid medium with hydroxylamine of which at least 70% is present in the form of a salt with a strong acid, the remainder, if any, being present as the free base or the salt of a weak acid.

Amino acids having masked amino groups react with amino acids having masked carboxyl groups to form peptide derivatives in good yields if the reaction medium contains an isonitrile. Isonitriles also are effective in causing condensation of amino acids having masked amino groups with compounds having active hydroxyl groups to the corresponding amino acid esters. The yields of the first-mentioned reaction are enhanced if the reaction mixture additionally contains one of the compounds having active hydroxyl groups. Both the peptide derivatives and the amino acid esters of the compounds having active hydroxyl groups are useful for peptide synthesis.

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Yokohama, Japan

Yasuo Ariyoshi