Preparation of d- and l-methionine from dl-methionine by enzymatic resolution.

It has been shown previously (1,2) that the synthesis of CO-NH linkages by papain as well as by other proteinases is characterized by extreme stereochemical specificity. Thus, upon the addition of cysteine-activated papain to a mixture of carbobenzoxy-nn-glutamic acid and aniline, there is formed carbobenzoxy-L-glutamic acid anilide, which separates in crystalline form. The carbobenzoxy-n-glutamic acid which remains in solution may then be hydrogenated to yield n-glutamic acid (2). As noted elsewhere (3), it appears desirable to examine the feasibility of this enzymatic resolution method for the preparation of the optically active isomers of several amino acids (methionine, threonine, valine, and isoleutine) whose DL forms are now readiiy accessible by synthesis. In the present communication there is described the preparation, by the enzymatic resolution of m-methionine, of Dand of L-methionine. A method for the resolution of nL-methionme has been described previously by Windus and Marvel (4), who used the classical procedure of Emil Fischer. Duschinsky and Jeannerat (5) prepared L-methionine from the racemate by the selective oxidation of the D isomer with n-amino acid oxidase. When carbobenzoxy-nn-methionine is incubated with aniline in the pres ence of cysteine-activated papain, carbobenzoxy-L-methionine anilide crystallizes with a yield of 95 per cent. From the filtrate, there may be isolated carbobenzoxy-n-methionine which, on catalytic hydrogenation, is converted to n-methionine of satisfactory purity. It was intended to obtain L-methionine by the hydrolysis of carbobenzoxy-L-methionine anilide with hydrochloric acid. The main product of the cleavage was found to be not L-methionine, however, but S-benzyl+ homocysteine. The formation of this compound from carbobenzoxy-Lmethionine anilide may be explained by assuming the formation of benzyl chloride in the course of the acid hydrolysis of the carbobenzoxy group, followed by the conversion of the thioether to a sulfonium ion. The preferential elimination of the methyl group during the decomposition of the