STEREOSELECTIVE DEUTERIUM-LABELING OF DIASTEREOTOPIC METHYL AND METHYLENE PROTONS OF L-LEUCINE

An asymmetric synthesis of regio-and stereoselectively deuterium-label led L-leucine was examined using 4-hydoxy-L-poline as a chiral templat e. An enol triflate of 4-oxoproline prepared from 4-hydroxyproline was effectively methylated by a Gilman reagent to afford a 4-methyl-3,4-d ehydroproline derivative. Then, a catalytic deuteration of the dehydro proline followed by RuO4-oxidation gave a deuterated 4-methylpyrogluta mic acid derivative that could easily be converted to (2S,3S,4R)-leuci ne-3,4,5,5-d(5) via a base-promoted ring opening and a reductive deute ration of the terminal carboxyl moiety. This strategy wits also applie d to the stereoselective synthesis of (2S,3S,4S)-[3,4,5,5,5-D-5]leucin e. (C) 1998 Elsevier Science Ltd. All rights reserved.