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

Abstract

Abstract An efficient syntheses of the 3′-N isomeric paclitaxel analogs, 4 and 5, are described. A highly diastereoselective Sharpless asymmetric dihydroxylation reaction is utilized to establish the required (2′R,3′S) stereochemistry on the C-13 side chain. Both of the 3′-N modified analogs 4 and 5 were found to be cytotoxic in vitro. Analog 4 also displayed comparable in vivo activity to that of paclitaxel in the ip M-109 tumor model.