Total Synthesis of (±)-Carquinostatin A, and Asymmetric Total Synthesis of (<i>R</i>)-(−)-Carquinostatin A and (<i>S</i>)-(+)-Carquinostatin A

Abstract

Total syntheses of (±)-carquinostatin A (1), and (R)-(-)-carquinostatin A (1a) together with its enantiomer, (S)-(+)-carquinostatin A (1b), possessing radical scavenging activity, were newly achieved. (±)-Carquinostatin A (1) was synthesized from 1-acetonyl-6-bromo-3-ethoxy-2-methylcarbazole (6), which was derived from the known 1-acetonyl-3-ethoxy-2-methylcarbazole (5). Introduction of a prenyl group at the 6-position of carbazole was successful in two steps. For the synthesis of (R)-(-)-carquinostatin A (1a) and (S)-(+)-carquinostatin A (1b), (R)-(-)-1-(2-acetoxypropyl)-3-hydroxy-2-methylcarbazole (15a) and (S)-(+)-3-hydroxy-1-(2-hydroxypropyl)-2-methylcarbazole (15b), prepared by lipase-QLM catalyzed enantioselective transesterification of 3-hydroxy-1-(2-hydroxypropyl)-2-methylcarbazole (14), were used as the chiral starting material.