TAXANE DITERPENES 4 - AUTOXIDATION, EPIMERIZATION AND ISOMERIZATION FOR THE INTRODUCTION OF FUNCTIONALITY INTO THE TAXANE ABC RING-SYSTEM

The bicyclo[5.4.0]undecenone 4 was converted through a four step seque nce involving activation, gem-methylcyclopropanation and reductive cle avage into 18 alpha/beta, containing the B/C rings of the taxanes. The A-ring has been attached to the B/C ring system by cyclization of the sulfone-ester 23 alpha to give 24. The A-ring was modified to give 29 , which underwent beta-elimination of the 3,10-oxido bridge via a dian ion, followed by transannular hydride shift to give the butenolide 30 and 32. Autoxidation of 30 gave 33 which was further elaborated into t he trans-fused B/C adduct 35. The isomeric 3,10-diones trans-39 and ci s-45 undergo autoxidation using t-BuOK/THF/O-2/P(OEt)(3) to give 2 and 46 respectively without B/C cis/trans isomerization. (C) 1998 Elsevie r Science Ltd. All rights reserved.