Enantioselective synthesis of the novel chiral sulfoxide derivative as a glycogen synthase kinase 3β inhibitor

Abstract

Glycogen synthase kinase 3β (GSK-3β) inhibitors are expected to be attractive therapeutic agents for the treatment of Alzheimer's disease (AD). Recently we discovered sulfoxides (S)-1 as a novel GSK-3β inhibitor having in vivo efficacy. We investigated practical asymmetric preparation methods for the scale-up synthesis of (S)-1. The highly enantioselective synthesis of (S)-1 (94% ee) was achieved by titanium-mediated oxidation with D-(-)-diethyl tartrate on gram scale. © 2010 Pharmaceutical Society of Japan.