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Totally Synthetic by Paul H. Docherty, 15 May 2006

Total Synthesis of Guanacastepene A & E


W. Shipe, E. J. Sorensen, J. Am. Chem. Soc. 2006, 128, 7025-7035.

DOI: 10.1021/ja060847g

Furthering their interest in the total synthesis of the Guanacastepenes, Sorensen et al have completed the synthesis of members A and D using an interesting fragmentation strategy. However, before this late-stage event, the A and C rings were constructed and united using a Stille cross-coupling. The required cyclobutane was then implaced via a photo-[2+2] cycloaddition:

With this in place, the cyclobutane was fragmented selectively to provide the seven-member ring, trapping with PhSeBr to facilitate elimination in the next step. A very reasonable explanation for this selectivity is given in detail in the paper.

This left the core of the guanacastepene series, from which a few simple steps returned guanacastepene A. However, a slight flaw in the synthesis concerns the resolution of an advanced fragment, taken from a racemic model study.