Synthesis of enantiomerically pure alpha-[14C]methyl-L-tryptophan

A practical method for the preparation of large amounts of enantiomerically pure alpha-[14C]methyl-L-tryptophan using the enzymatic resolution of the corresponding D,L-methyl ester is reported. The radiolabelled alpha-methyl group was introduced using the alpha-methylation of the lithium enolate of the Schiff base of L-tryptophan methyl ester. Hydrolysis of the Schiff base with 1N HCl provided the D,L-methyl ester of alpha-[14C]methyl tryptophan. Enantioselective enzymatic hydrolysis of the L-methyl ester by alpha-chymotrypsin gave the enantiomerically pure alpha-[14C]methyl-L-tryptophan. The overall yield of this preparation was 33%.