Synthesis and biological evaluation of 3'-N-thiocarbamate paclitaxel derivatives

Paclitaxel is a natural occurring diterpene alkaloid originally isolated from the bark of Taxus brevifolia. It is now one of the most important chemotherapeutic agents for clinical treatment of ovarian and breast cancer for the past decades. Recent clinical trials have also shown paclitaxel's potential for the treatment of non-small-cell lung cancer, and other types of cancers. While tremendous chemical research efforts have been made in the past years, which established the fundamental structure-activity relationships of the paclitaxel, and have provided analogs for biochemical studies to elucidate the precise mechanism of action for the development of second-generation agents, many areas remain to be explored. One of the principal goals associated with research is the identification of the structural features of Ttaxol required for its biochemical and physiological performance. Ultimately, such research can be expected to the identification of structurally simpler and clinically more effective analogues. A large number of analogues prepared by other have incorporated modifications at the side chain 3'-N position, and some compounds with such modifications are clinical trials. In continuation of the studies on the structure/activity relationships of paclitaxel analogues, we now report the synthesis of novel sulfur containing paclitaxel side-chain analogues