CONVERGENT CATALYTIC ASYMMETRIC-SYNTHESIS OF CAMPTOTHECIN ANALOG GI147211C

The topoisomerase I inhibitor G1147211C (4) was discovered at Glare We llcome and shown to have promising anti-cancer properties. In order to fully assess the clinical potential of 3, an improved synthesis of th e: drug substance was required. Herein is described a convergent catal ytic asymmetric synthesis of 4 which utilizes as key steps, two Heck r eactions, a Sharpless asymmetric dihydroxylation reaction, and a Mitsu nobu reaction. A 2-chloroquinoline is shown to be a viable substrate f or the final Heck reaction to generate the camptothecin nucleus. (C) 1 997 Elsevier Science Ltd.