Synthesis, biological activity, and structure-activity relationship (SAR) study of novel 3-prime-alkyl, 3-prime-alkenyl, and 3-prime-fluorinated taxoids.

摘要

Paclitaxel, and its semi-synthetic analog, docetaxel, are potent antimitotic agents which exhibit strong activity against various cancers through a unique mechanism of action. They are considered two of the leading clinical chemotherapeutic agents for advanced ovarian and breast cancer in the United States. This thesis comprises several aspects of our continuing structure-activity relationship studies of several series of novel modified taxoids.;The synthesis and bio-evaluation of a series of C-3;Chapter 3 highlights the synthesis of new docetaxel analogs derived from 14;The development of several series of C-3;Chapter 1 provides an overview of the discovery of paclitaxel and docetaxel, their mode of action with respect to cellular replication, and complications associated with their clinical application. The efficient synthesis of side chain precursors via the chiral ester enolate-imine cyclocondensation reaction and subsequent application towards the synthesis of paclitaxel and docetaxel are also described.