ChemInform Abstract: Enzymatic Resolution of 2-Substituted Tetrahydroquinolines. Convenient Approaches to Tricyclic Quinoxalinediones as Potent NMDA-Glycine Antagonists

Two approaches leading to the enantiomerically pure tricyclic quinoxalinedione class of NMDA-glycine antagonists using enzymatic resolutions are described. An intermediate, racemic methyl 1,2,3,4-tetrahydroquinoline-2-carboxylate 3 , was resolved to ( S )- 3 in 97% ee and 47% yield (E=67) using α-chymotrypsin. In an improved method, hydrolysis of another intermediate, racemic methyl 1,2,3,4-tetrahydroquinoline-2-acetate 4 , with Novozym ® 435 provided the desired ( S )- 4 in high enantioselectivity and yield (93% ee, 50%, E=94).