A facile chemoenzymatic approach to chiral non-racemic beta-alkyl-gamma-amino acids and 2-alkylsuccinic acids. A concise synthesis of (S)-(+)-Pregabalin

摘要

Both enantiomerically pure antipodes of GABA analogues were prepared as hydrochloride salts, by enzymatic kinetic resolution of their precursors ethyl 2-(nitromethyl)alkanoates. These latter compounds can be easily transformed into enantiomerically pure 2-alkylsuccinic acids by a Nef reaction followed by oxidation. Interestingly, this reaction was particularly easy for the neopentyl derivative (S)-(+)-7d, which underwent conversion into its corresponding succinic acid derivative (S)-(-)-8d in buffered solution. The absolute configurations of the main Compounds of interest involved are given, together with their CD spectra. (C) 2008 Elsevier Ltd. All rights reserved.