Stereocontrolled Total Synthesis of (+)-Leucascandrolide A

Authors


  • We thank the EPSRC (studentship to M.T. and GR/N08520), the EU (Network HPRN-CT-2000-00018), and Merck, Pfizer, and Novartis for support.

Abstract

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Apparently no longer available from its natural source is the potent cytotoxic and antifungal agent leucascandrolide A (1), which was initially isolated from a New Caledonian calcareous sponge. A highly stereocontrolled total synthesis of this structurally unique macrolide commences with a Jacobsen asymmetric hetero Diels–Alder reaction to configure the tetrahydropyran ring. An efficient endgame relies on two Mitsunobu reactions, the first to generate the 18-membered macrolactone and the second to attach the oxazole-bearing side chain.

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