Convergent catalytic asymmetric synthesis of camptothecin analog GI147211C

Abstract The topoisomerase I inhibitor GI147211C ( 4 ) was discovered at Glaxo Wellcome and shown to have promising anti-cancer properties. In order to fully assess the clinical potential of 4 , an improved synthesis of the drug substance was required. Herein is described a convergent catalytic asymmetric synthesis of 4 which utilizes as key steps, two Heck reactions, a Sharpless asymmetric dihydroxylation reaction, and a Mitsunobu reaction. A 2-chloroquinoline is shown to be a viable substrate for the final Heck reaction to generate the camptothecin nucleus.