title: Enantioselective synthesis of the novel chiral sulfoxide derivative as a glycogen synthase kinase 3beta inhibitor.
abstract: Glycogen synthase kinase 3beta (GSK-3beta) 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-3beta 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.
authors.affiliation: Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co, Ltd, Osaka 532-8686, Japan. Saitoh_Morihisa@takeda.co.jp
authors.forename: Morihisa
authors.initials: M
authors.lastname: Saitoh
authors.forename: Jun
authors.initials: J
authors.lastname: Kunitomo
authors.forename: Eiji
authors.initials: E
authors.lastname: Kimura
authors.forename: Toru
authors.initials: T
authors.lastname: Yamano
authors.forename: Fumio
authors.initials: F
authors.lastname: Itoh
authors.forename: Masakuni
authors.initials: M
authors.lastname: Kori
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007536:Isomerism; D010084:Oxidation-Reduction; D012451:Safrole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D012451:Safrole; C005746:sulfoxide