| In the past twenty years few natural products have created a greater impact in the areas of clinical oncology and biomedical research than Taxol ®. Its FDA-approved use in the treatment of metastatic breast and ovarian cancers constitutes one of the major breakthroughs in chemotherapy today; it is currently the number-one selling anticancer drug in the world. Taxol, the primary representative of a new class of compounds called taxoids, was first isolated from the bark of the Pacific yew tree, Taxus brevifolia , in 1969; its complex structure was elucidated two years later by Wall and Wani. The discovery in 1979 by Horwitz and coworkers describing the unique mechanism by which taxol inhibits cell replication has since served as an impetus for intense pharmacological studies aimed at its therapeutic development. Our synthetic strategy for constructing the carbocyclic core of taxol and other Taxus diterpenes will be presented herein. It involves as a key step the reaction between a Fischer carbene complex and a chiral 1,6-enyne to construct bicyclo[3.1.1]heptanones as taxane A-ring synthons. |
