Lipase-Catalyzed Asymmetric Synthesis of Desprenyl-carquinostatin A and Descycloavandulyl-lavanduquinocin

Abstract

An asymmetric synthesis of the core carbazole structure, 6-desprenyl-carquinostatin 3 and 6-descycloavandulyl-lavanduquinocin 3, toward a total synthesis of carquinostatin A (1) and lavanduquinocin (2), has been established. Lipase QLM (Meito) catalyzed enantioselective acetylation of the racemic alcohol 6 gave the (−)-acetate 7 and the (+)-alcohol 6 with high enantioselectivity. The absolute stereochemistry of the (−)- and (+)-alcohol 6 have been determined to be R- and S-configurations, respectively, by the advanced Mosher method. In the same manner, the (−)-acetate 13 and the (+)-alcohol 12 have been obtained from the racemic alcohol 12. The (R)-(−)-acetate 13, derived from the (R)-(−)-acetate 7, was the same as the (−)-acetate 13, which has been determined to be (R)-configuration. Oxidation of the (R)-(−)-acetate 13 followed by hydrolysis afforded (R)-(−)-6-desprenyl-carquinostatin [and (R)-(−)-6-descycloavandulyl-lavanduquinocin] 3. In addition, oxidation of the (S)-(+)-alcohol 12 provided (S)-(+)-3, which is the enantiomer of 6-desprenyl-carquinostatin A (R)-(−)-3.