Total Synthesis of Myxalamide A

Anna K. Mapp and Clayton H. Heathcock*
Department of Chemistry, University of California, Berkeley, California 94720
J. Org. Chem., 1999, 64 (1), pp 23–27
DOI: 10.1021/jo9813742
Publication Date (Web): December 11, 1998
Copyright © 1999 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

Abstract

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The polyene antibiotic myxalamide A (1) has been prepared by total synthesis. The synthesis illustrates a useful strategy for synthesis in which the high 1,2-stereocontrol achievable with the aldol reaction can be parlayed by other stereoselective processes so as to give compounds having two or more stereocenters with remote relationships. Application of the Evans asymmetric aldol reaction to aldehyde 13 gives the β-hydroxy imide 17. Because the substrate is an α,β-unsaturated aldehyde, the alcohol is allylic. After suitable functional group manipulation, this allylic alcohol is subjected to enolate Claisen rearrangement (as propionate 22) to give allylsulfide 23, having three stereocenters with a 1,4,5-relationship. Further functional group manipulation and one-carbon homologation converts this intermediate into 26, which is oxidized and subjected to Evans−Mislow allylsulfoxide rearrangement to obtain 27, having three stereocenters with a 1,2,5-relationship. The synthesis of myxalamide A was completed by converting aldehyde 30 into dienyne 40. Alkyne 40 was hydroborated with catechol borane, and the resulting E-vinylborane was subjected to Suzuki coupling with the Z-iodo triene 9 to provide myxalamide A (1).

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History

  • Published In Issue January 08, 1999
  • Received July 14, 1998

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