Total Synthesis of Clavilactones

Kenichi Takao, Kento Mori, Kenya Kasuga, Ryuki Nanamiya, Ayumi Namba, Yuuki Fukushima, Ryuichi Nemoto, Takuma Mogi, Hiroyuki Yasui, Akihiro Ogura, Keisuke Yoshida, Kin Ichi Tadano

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Clavilactones A, B, and D are epidermal growth factor receptor tyrosine kinase inhibitors that were isolated from cultures of the fungus Clitocybe clavipes. Here, we report full details of the total synthesis of these clavilactones. A key feature of our synthetic approach is a ring-opening/ring-closing metathesis strategy that allows the concise transformation of a cyclobutenecarboxylate into a γ-butenolide. Coupled with enantioselective Ti/BINOL-catalyzed alkynylation of a multisubstituted benzaldehyde and ring-closing metathesis of a diene-bearing silylene acetal to construct the 10-membered carbocycle, this strategy enabled the total synthesis of the natural enantiomers (+)-clavilactone A and (-)-clavilactone B. In addition, the correct structure of clavilactone D was determined by the synthesis of two newly proposed structures. This research resulted in the asymmetric synthesis of the revised (+)-clavilactone D.

Original languageEnglish
Pages (from-to)7060-7075
Number of pages16
JournalJournal of Organic Chemistry
Volume83
Issue number13
DOIs
Publication statusPublished - 2018 Jul 6

Fingerprint

Bearings (structural)
Acetals
Enantiomers
Fungi
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
clavilactone A
clavilactone D
clavilactone B
butenolide
naphthol BINOL
benzaldehyde

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Takao, K., Mori, K., Kasuga, K., Nanamiya, R., Namba, A., Fukushima, Y., ... Tadano, K. I. (2018). Total Synthesis of Clavilactones. Journal of Organic Chemistry, 83(13), 7060-7075. https://doi.org/10.1021/acs.joc.7b03268

Total Synthesis of Clavilactones. / Takao, Kenichi; Mori, Kento; Kasuga, Kenya; Nanamiya, Ryuki; Namba, Ayumi; Fukushima, Yuuki; Nemoto, Ryuichi; Mogi, Takuma; Yasui, Hiroyuki; Ogura, Akihiro; Yoshida, Keisuke; Tadano, Kin Ichi.

In: Journal of Organic Chemistry, Vol. 83, No. 13, 06.07.2018, p. 7060-7075.

Research output: Contribution to journalArticle

Takao, K, Mori, K, Kasuga, K, Nanamiya, R, Namba, A, Fukushima, Y, Nemoto, R, Mogi, T, Yasui, H, Ogura, A, Yoshida, K & Tadano, KI 2018, 'Total Synthesis of Clavilactones', Journal of Organic Chemistry, vol. 83, no. 13, pp. 7060-7075. https://doi.org/10.1021/acs.joc.7b03268
Takao K, Mori K, Kasuga K, Nanamiya R, Namba A, Fukushima Y et al. Total Synthesis of Clavilactones. Journal of Organic Chemistry. 2018 Jul 6;83(13):7060-7075. https://doi.org/10.1021/acs.joc.7b03268
Takao, Kenichi ; Mori, Kento ; Kasuga, Kenya ; Nanamiya, Ryuki ; Namba, Ayumi ; Fukushima, Yuuki ; Nemoto, Ryuichi ; Mogi, Takuma ; Yasui, Hiroyuki ; Ogura, Akihiro ; Yoshida, Keisuke ; Tadano, Kin Ichi. / Total Synthesis of Clavilactones. In: Journal of Organic Chemistry. 2018 ; Vol. 83, No. 13. pp. 7060-7075.
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