Preparation of the optically active isomers of S-benzylhomocysteine by enzymatic resolution.

S-Benzylhomocysteine, containing isotopic atoms, has proved to be a key intermediate in the synthesis of labeled methionine and related compounds (1). The need of the optically active isomers of these tagged compounds for various metabolic investigations has prompted us to work out a method for the resolution of S-benzylhomocysteine which would be particularly suitable for small quantities of S-benzylhomocysteine likely to be used in syntheses of this compound labeled with isotopes. The success which attended the use of papain in the resolution of DLmethionine by Dekker and Fruton (2) encouraged us to explore the possibilities of this method for the preparation of the optically active isomers of S-benzylhomocysteine. When N-acetyl-S-benzyl-nn-homocysteine was incubated with aniline in the presence of cysteine-activated papain, Nacetyl-S-benzyl-n-homocysteine anilide crystallized in high yield. From the filtrate, there could be isolated N-acetyl-S-benzyl-n-homocysteine also in excellent yield. Recrystallization to satisfactory rotation gave a yield of 80 per cent for the L isomer and 89 per cent for the D isomer. Acid hydrolysis of these isomers has produced S-benzyl-n-homocysteine and S-benzyl-n-homocysteine of satisfactory purity in excellent yields. This enzymatic resolution method is equally effective with large or small amounts of S-benzyl-nn-homocysteine. S-Benzyl-n-homocysteine has previously been prepared by du Vigneaud and Patterson (3) through the fractional crystallization of the brucine salts of the N-formyl derivatives of S-benzyl-nn-homocysteine. Marc recently, Dekker and Fruton (2) obtained S-benzyl-n-homocysteine by the acid hydrolysis of carbobenzoxy-n-methioninanilide from the enzymatic resolution of carbobenzoxy-nn-methionine.