Absolute stereochemical assignment and fluorescence tuning of the small molecule tool, (-)-blebbistatin

Cristina Lucas-Lopez, Stephen Patterson, Till Blum, Aaron F. Straight, Judit Toth, Alexandra M.Z. Slawin, Timothy J. Mitchison, James R. Sellers, Nicholas J. Westwood

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

(-)-Blebbistatin (1), a recently discovered small molecule inhibitor of the ATPase activity of non-muscle myosin II has been prepared from methyl 5-methylanthranilate (6) in three steps. This flexible synthetic route has also been used to prepare a nitro group-containing analogue 12 that has modified fluorescence properties and improved stability under microscope illumination. The key step in the synthesis of 1 and its analogues was the asymmetric hydroxylation of the quinolone intermediate 3 using the Davis oxaziridine methodology. The absolute stereochemistry of (-)-blebbistatin (1) was shown to be S by X-ray crystal structure analysis of a heavy atom (bromine) containing analogue 11, which was subsequently reduced and shown to be identical to 1.

Original languageEnglish
Pages (from-to)1736-1740
Number of pages5
JournalEuropean Journal of Organic Chemistry
Issue number9
DOIs
Publication statusPublished - Apr 29 2005

Keywords

  • Asymmetric synthesis
  • Fluorescence
  • Inhibitors

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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    Lucas-Lopez, C., Patterson, S., Blum, T., Straight, A. F., Toth, J., Slawin, A. M. Z., Mitchison, T. J., Sellers, J. R., & Westwood, N. J. (2005). Absolute stereochemical assignment and fluorescence tuning of the small molecule tool, (-)-blebbistatin. European Journal of Organic Chemistry, (9), 1736-1740. https://doi.org/10.1002/ejoc.200500103