An Enantioselective Synthesis of FR182877 Provides a Chemical Rationalization of Its Structure and Affords Multigram Quantities of Its Direct Precursor
Document Type
Article
Department
Chemistry (HMC)
Publication Date
2003
Abstract
The evolution of a strategy culminating in an efficient, enantioselective synthesis of the potent microtubule-stabilizing agent FR182877 is described. Guided by a proposed biogenesis of this complex natural product, a solution emerged that involved the first reported example of a double transannular Diels−Alder reaction to fashion the key elements of its hexacyclic structure. This pivotal transformation creates a complex pentacycle from a 19-membered macrocyclic pentaene, forming seven new stereogenic centers in a fully diastereocontrolled fashion. The efficiency of the approach ultimately enabled the preparation of multigram quantities of the direct precursor of FR182877 for conversion to the relatively unstable natural product when required. The reactivity of the strained, bridgehead olefin of this secondary metabolite with biologically relevant nucleophiles is also described.
Rights Information
© 2003 American Chemical Society
DOI
10.1021/ja021472b
Recommended Citation
“An enantioselective synthesis of FR182877 provides a chemical rationalization of its structure and affords multigram quantities of its direct precursor,” Vanderwal, C.D.; Vosburg, D.A.; Weiler, S.; Sorensen, E.J. J. Am. Chem. Soc. 2003, 125, 5393-5407. DOI: 10.1021/ja021472b
