STRUCTURE-ACTIVITY-RELATIONSHIPS STUDY AT THE 3'-N POSITION OF PACLITAXEL - PART 1 - SYNTHESIS AND BIOLOGICAL EVALUATION OF THE 3'-(T)-BUTYLAMINOCARBONYLOXY BEARING PACLITAXEL ANALOGS

An efficient syntheses of the 3'-N isomeric paclitaxel analogs, 4 and 5, are described. A highly diastereoselective Sharpless asymmetric dih ydroxylation reaction is utilized to establish the required (2'R, 3'S) stereochemistry on the C-13 side chain. Both of the 3'-N modified ana logs 4 and 5 were found to be cytotoxic in vitro. Analog 4 also displa yed comparable in vivo activity to that of paclitaxel in the ip M-109 tumor model. (C) 1997 Elsevier Science Ltd.