In 1996 the Wender Group succeeded in "total synthesis" of Taxol (meaning they figured out how to create it from scratch in the laboratory). Their work helped pave the way for Taxol—now produced via "semi-synthesis" using some material from renewable yew trees—to become the best-selling cancer-fighting drug in history, saving countless lives and leaving the scarce stands of Pacific yews intact.
In the four total syntheses to date two clearly differentstrategies have been demonstrated. Thus, Nicolaou and Danishefskyboth utilised a convergent approach to form the 'B' ring by anintramolecular cyclisation whereas both Holton and Wender used linearroutes, with the central 'ABC' ring system being formed by thefragmentation of the highly strained bicyclic systems. A commonfeature of all the syntheses is the use of a C1, C2 cyclic carbonateto introduce the hydroxybenzoate functionality. In the two convergentsyntheses the carbonate also has the added advantage of preorganisingthe structure for cyclisation.
Key features of the structure of Taxol (Figure 1) thatrequire careful consideration by the synthetic chemist attempting atotal synthesis are, the sterically congested double bond containing'A' ring, the central eight membered 'B' ring and the oxetane 'D'ring. The high degree of oxygenation present in a range of oxidationstates, coupled with the 9 asymmetric centres means that Taxolpresents an interesting challenge to synthetic chemists.