Chemo-enzymatic synthesis of ( R)-(+)-aminoglutethimide by kinetic resolution of (±)-4-cyano-4-phenyl-1-hexanol

Abstract

Chemo-enzymatic approaches for the synthesis of the family of aromatase inhibitory drug via lipase-catalyzed kinetic resolution of (±)-4-cyano-4-phenyl-1-hexanol ( 2) as appropriate precursors were described. Enzymatic transesterification of primary alcohol (±)- 2 using Pseudomonas cepacia (Amano PS, PCL) provided the enantiopure alcohol ( R)-(−)- 2 with 99% ee at conversion of 86%, while that of (±)- 2 using Pseudomonas fluorescens (Amano AK, LAK) provided the ( S)-(+)- 2 with 96% ee at conversion of 86%. Chemical transformation of substrate ( R)-(−)- 2 gave ( R)-(+)-aminoglutethimide ( 1) in enantioselectively high yield.