Total synthesis of bafilomycin A1

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

Research output: Contribution to journalArticle

72 Citations (Scopus)

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

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Lactones
Vacuolar Proton-Translocating ATPases
Macrolides
Ketones
Aldehydes
Hydroxyl Radical
Anti-Bacterial Agents
Glucose
bafilomycin A1
methyl lactate
vinyl iodide
3-hydroxybutanal

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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

Total synthesis of bafilomycin A1. / Toshima, Kazunobu; Jyojima, T.; Yamaguchi, H.; Noguchi, Y.; Yoshida, T.; Murase, H.; Nakata, M.; Matsumura, S.

In: Journal of Organic Chemistry, Vol. 62, No. 10, 1997, p. 3271-3284.

Research output: Contribution to journalArticle

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, vol. 62, no. 10, pp. 3271-3284. https://doi.org/10.1021/jo970314d
Toshima K, Jyojima T, Yamaguchi H, Noguchi Y, Yoshida T, Murase H et al. Total synthesis of bafilomycin A1. Journal of Organic Chemistry. 1997;62(10):3271-3284. https://doi.org/10.1021/jo970314d
Toshima, Kazunobu ; Jyojima, T. ; Yamaguchi, H. ; Noguchi, Y. ; Yoshida, T. ; Murase, H. ; Nakata, M. ; Matsumura, S. / Total synthesis of bafilomycin A1. In: Journal of Organic Chemistry. 1997 ; Vol. 62, No. 10. pp. 3271-3284.
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