Total synthesis of bafilomycin A1

K. Toshima, T. Jyojima, H. Yamaguchi, Y. Noguchi, T. Yoshida, H. Murase, M. Nakata, S. Matsumura

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Abstract

The highly stereoselective total synthesis of the macrolide antibiotic, bafilomycin A1 (1), the first specific potent inhibitor of vacuolar H+-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 16-membered tetraenic lactone and β-hydroxyl hemiacetal side-chain subunits. The C1-C17 16-membered lactone aldehyde 2 was synthesized through the coupling of the C5-C11 vinyl iodide 4 and the C12-C17 vinylstannane 5, followed by construction of the C1-C4 diene and macrolactonization. The aldol coupling of 2 and the C18-C25 ethyl ketone 3 followed by desilylation provided 1, which was identical with natural bafilomycin A1. The key synthetic segments 3-5 were effectively synthesized from the readily available chiral materials, D-glucose, ethyl (S)-lactate, and methyl (S)-3-hydroxy-2-methylpropionate, respectively.

Original languageEnglish
Pages (from-to)3271-3284
Number of pages14
JournalJournal of Organic Chemistry
Volume62
Issue number10
DOIs
Publication statusPublished - 1997 Jan 1

ASJC Scopus subject areas

  • Organic Chemistry

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    Toshima, K., Jyojima, T., Yamaguchi, H., Noguchi, Y., Yoshida, T., Murase, H., Nakata, M., & Matsumura, S. (1997). Total synthesis of bafilomycin A1. Journal of Organic Chemistry, 62(10), 3271-3284. https://doi.org/10.1021/jo970314d