Total synthesis of (+)-schweinfurthins B and E

Joseph J. Topczewski, Jeffrey D. Neighbors, David F. Wiemer

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

(Chemical Equation Presented) The first total synthesis of (+)-schweinfurthin B, a potent and differentially active cytotoxic agent, has been accomplished. Completion of the synthesis required just 16 steps in the longest linear sequence from commercially available vanillin. Key synthetic transformations included a Shi epoxidation and an efficient cascade cyclization initiated by treatment of the resulting epoxide with BF3· OEt2. Furthermore, use of a methyl ether as a stable protecting group for benzylic alcohols dramatically increased the efficiency of the overall sequence. The benzylic ether can be removed from this electron-rich aromatic system through oxidation with DDQ that provided the desired aldehyde intermediate in quantitative yield and shortened the synthetic sequence. Introduction of the A-ring diol in the required cis stereochemistry then became viable through a short sequence highlighted by an aldol condensation with benzaldehyde to introduce an olefin as a latent carbonyl group at the C-3 position. This synthesis established for the first time the absolute stereochemistry of the natural product, and provides access to material on a scale that will advance biological studies. The total synthesis of the closely related compound (+)-schweinfurthin E also is reported.

Original languageEnglish (US)
Pages (from-to)6965-6972
Number of pages8
JournalJournal of Organic Chemistry
Volume74
Issue number18
DOIs
StatePublished - Sep 18 2009

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