Diverted total synthesis: preparation of a focused library of latrunculin analogues and evaluation of their actin-binding properties.

ABSTRACT: Two largely catalysis-based and highly convergent total syntheses of latrunculin A (1) and B (2) were diverted to the preparation of a focused library of analogues of these potent actin-binding macrolides that enjoy widespread use in chemical biology. Because the chosen route allows for structural variations of all characteristic parts of the natural leads, it was possible to map the previously largely unknown structure/activity profile of this class of bioactive natural products. This led to the discovery that the removal of the methyl branches decorating the macrocycle in 2 engenders a significant increase in potency, while streamlining the synthesis to a considerable extent. Moreover, compelling evidence is provided that the conspicuous 2-thiazolidinone ring present in all naturally occ

SUBMITTER: Furstner A 

PROVIDER: S-EPMC1149423 | biostudies-literature | 2005 Jun

REPOSITORIES: biostudies-literature