Enantioselective Synthesis of the Novel Chiral Sulfoxide Derivative as a Glycogen Synthase Kinase 3β Inhibitor

• Published in: Chemical and Pharmaceutical Bulletin Vol. 58; no. 9; pp. 1252 - 1254
• Main Authors: Saitoh, Morihisa, Kunitomo, Jun, Kimura, Eiji, Yamano, Toru, Itoh, Fumio, Kori, Masakuni
• Format: Journal Article
• Language: English
• Published: The Pharmaceutical Society of Japan 01-09-2010
• Subjects: Alzheimer's disease; enantioselective oxidation; glycogen synthase kinase 3β
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.58.1252

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.