CHEMOENZYMATIC SYNTHESIS OF ISOTOPICALLY LABELED L-VALINE, L-ISOLEUCINE AND ALLO-ISOLEUCINE

Syntheses of (3R)-[4,4,4-D-3]-L-valine, [N-15]-L-isoleucine and [N-15] -allo-isoleucine from homochiral 2-alkylated carboxylic acids are desc ribed, The approach involves a one-carbon homologation of the carboxyl ic acid to give the corresponding beta-substituted alpha-keto ester wh ich is converted directly to the alpha-amino acid in a one-pot procedu re involving two enzyme catalysed reactions (Candida cylindracea lipas e to hydrolyse the ester and leucine dehydrogenase to catalyse the red uctive amination of the ketone). This strategy may be simply adapted f or the selective labelling of each site of the L-amino acid.