Enantioselective synthesis of the novel chiral sulfoxide derivative as a glycogen synthase kinase 3beta inhibitor.
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.
Saitoh
Morihisa
M
Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co, Ltd, Osaka 532-8686, Japan. Saitoh_Morihisa@takeda.co.jp
Kunitomo
Jun
J
Kimura
Eiji
E
Yamano
Toru
T
Itoh
Fumio
F
Kori
Masakuni
M
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
D004791:Enzyme Inhibitors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D012451:Safrole; C005746:sulfoxide