Asymmetric synthesis of a cyclopropanecarboxylic acid derivative – the potential agonist/antagonist of GABA receptors

Abstract

The synthesis of enantiomerically pure (1S,2S,S P)-1-[hydroxy(methyl)phosphonyl]-2-aminocyclopropanecarboxylic acid (1) (a potential agonist/antagonist of GABA receptors) was accomplished in six steps based on optically inactive methyl 2-[methoxy(methyl)phosphonyl]acrylate (2). The key steps of this synthesis included the cyclopropane ring formation by the asymmetric cyclopropanation reaction of 2 with (S)-dimethylsulfonium(p-tolylsulfinyl)methylide (3), regio and stereoselective installation of ethoxycarbonyl group in the cyclopropane ring, and the chemoselective desulfinylation reaction conducted with phenylsilane under the basic conditions.