The major objective of this research is to make significant contributions to organic chemistry and medicine through synthetic studies towards the taxane class of natural products, specifically focused on the antitumor alkaloid taxol. Our research efforts will be focused on the development of a practical, general, and flexible total synthesis of taxol for two purposes: (1) to secure a large scale supply of taxol or the most effective taxol analogue for clinical use and (2) to provide a wide variety of taxol analogues for structure/activity studies in order to identify the most effective taxol analogue. Experimentally, we plan to construct the ring B of taxol at the very late stage of synthesis by using the Ni(II)/Cr(Il)-mediated coupling reaction in a simultaneous or step-wise manner. Obvious advantages of this approach include a high degree of convergence and flexibility and a minimum number of steps required for the functional group manipulation after the key coupling reaction. By using a model system, we have demonstrated the feasibility of this approach.
