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Absolute Stereochemical Assignment and Fluorescence Tuning of the Small Molecule Tool, (–)‐Blebbistatin

2005; Wiley; Volume: 2005; Issue: 9 Linguagem: Inglês

10.1002/ejoc.200500103

1434-193X

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

Enzyme Structure and Function

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 . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)