Convergent catalytic asymmetric synthesis of camptothecin analog GI147211C

The topoisomerase I inhibitor G1147211C (4) was discovered at Glare Wellcome and shown to have promising anti-cancer properties. In order to fully assess the clinical potential of 3, 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. (C) 1997 Elsevier Science Ltd.