Total Synthesis and Configurational Assignment of (−)-Dictyostatin, a Microtubule-Stabilizing Macrolide of Marine Sponge Origin

Authors


  • This research was supported by the EPSRC, the NSERC-Canada (R.B.), the Gobierno de Canarias, the Cambridge European Trust (O.D.), the EC (Network HPRN-CT-2000-18 and IE Marie Curie Fellowship to K.G.P.), Novartis Pharma AG, and the Merck Research Council. We thank Dr. Amy Wright (Harbor Branch Oceanographic Institution) for helpful discussions and for providing an authentic sample of dictyostatin, and Kate Ashton (Cambridge) for molecular modeling assistance.

Abstract

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A flexible and modular approach was used in the convergent and highly stereocontrolled synthesis of the antimitotic agent dictyostatin. This first total synthesis establishes its full stereochemistry and should be amenable to producing useful quantities and designed analogues of this molecule, whose conformation closely resembles that of discodermolide (see overlayed structures).

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