Total Synthesis Highlights

The cyclization of 2 to 11 proceeded smoothly, as did the alkylation of 11 to 12. The
diastereoselectivity of the alkylation followed from the conformational bias of the ring system.
The conversion of the terminal alkene to the acid 13 initially was troublesome, but a solution was
found in metathesis with vinyl boronate followed by oxidation. Coupling with 11 followed by
deprotection then gave 3.
The absolute configuration of the tricyclic core of 3 was set in the intramolecular ene cyclization
of 6 to 7. There is the possibility that with an enantiomerically-pure catalyst, the product 7 and so
3 could be prepared in high enantiomeric excess.
Total syntheses of platensimycin 3 are underway in several other research groups. The diversity of
the approaches being explored will enrich organic synthesis.
48. The Sorensen Synthesis of (-)-Guanacastepene E
The guanacastepenes, of which guanacastepene E (3) is representative, initially elicited excitement
because of their activity against drug resistant bacterial strains. Although the systemic toxicity of
the guanacastepenes has cooled that enthusiasm, the guanacastepenes remain as architectural
challenges. In particular, a convergent synthesis plan requires the development of a strategy for
constructing the central 7-membered ring with control of relative and absolute configuration,
particularly of the two angularly methylated quaternary centers. Erik J. Sorensen of Princeton
University (J. Am. Chem. Soc. 2006, 128, 7025.) solved this problem by the intramolecular
photochemical dimerization of 1, which delivered 2 with high diastereocontrol. Directed ring
fragmentation then led to 3.