Alternative Metathesis Approaches to the Epothilones

When such problems are encountered in synthesis, a golden opportunity exists to develop insightful and thought-provoking solutions. The recent successful metathesis-based approach by 

In addition to this elegant reformulation of the metathesis strategy toward the epothilones, an equally intriguing and challenging 

While both this synthesis and the previous example by Fiirstner are certainly important for the epothilone field by providing stereospecific constructions of 1 and 2, the perhaps more important feature is their beautiful illustration of the synergistic relationship between catalyst design and subsequent application in complex molecule synthesis. Key to the success of each approach was the development of a catalyst system that could reduce these creative metathesis designs to practice. As the scope of 94 and 16 as metathesis initiators is explored further, buttressed by the addition of more powerful catalysts than these systems, the range of metathesis-based applications in natural product synthesis should become even more spectacular. 

Sheehan, The Enchanted Ring The Untold Story of Penicillin, MIT Press, Cambridge, 1982, p. 224 b) S. Selwyn, R. W. Lacey, M. Bakhtiar, The Beta-Lactam Antibiotics Penicillins and Cephalosporins in Perspective, Hodder and Stoughton, London, 1980, p. 364. 

For some discussion of this topic, see R.H. Grubbs, Prog. Inorg. Chem. 1978, 24, 1. 

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