Copper-Catalyzed Asymmetric Synthesis and Comparative Aldose Reductase Inhibition Activity of (+)/(−)-1,2-Benzothiazine-1,1-dioxide Acetic Acid Derivatives

Abstract

A copper catalyst system for the asymmetric 1,4-hydrosilylation of the α,β-unsaturated carboxylate class was developed by which synthesis of (+)- and (-)-enantiomers of 1,2-benzothiazine-1,1-dioxide acetates has been achieved with a good yield and an excellent level of enantioselectivity. A comparative structure-activity relationship study yielded the following order of aldose reductase inhibition activity: (-)-enantiomers > racemic > (+)-enantiomers. Further, a molecular docking study suggested that the (-)-enantiomer had significant binding affinity and thus increased inhibition activity.