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

• Published in: Journal of organic chemistry Vol. 79; no. 11; pp. 4963 - 4972
• Main Authors: Parveen, Shagufta, Hussain, Saghir, Qin, Xiangyu, Hao, Xin, Zhu, Shaojuan, Rui, Miao, Zhang, Shuzhen, Fu, Fengyan, Ma, Bing, Yu, Qun, Zhu, Changjin
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 06.06.2014; Amer Chemical Soc
• Subjects: Acetates - chemical synthesis; Acetates - chemistry; Acetic Acid - chemistry; Aldehyde Reductase - antagonists & inhibitors; Aldehyde Reductase - chemistry; Aldehydes - chemistry; Catalysis; Chemistry; Chemistry, Organic; Copper; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Physical Sciences; Science & Technology; Stereoisomerism; Thiazines - chemical synthesis; Thiazines - chemistry; POTENT; DESIGN; 1,1-DIOXIDE; ENANTIOSELECTIVE CONJUGATE REDUCTION
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo500338c

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.