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Leucascandrolide A: Synthesis and Related Studies

2003; American Chemical Society; Volume: 68; Issue: 24 Linguagem: Inglês

10.1021/jo034964v

1520-6904

Alec Fettes, Erick M. Carreira,

Marine Toxins and Detection Methods

The total synthesis of the biologically active marine natural product leucascandrolide A is reported. A convergent strategy is employed, allowing for the rapid assembly of the macrolide moiety. Key steps of our approach include the diastereoselective addition of a zinc alkynilide to (R)-isopropylidene glyceraldehyde, the enantioselective copper(I) fluoride catalyzed aldol addition of a TMS-dienolate to crotonaldehyde, and the formation of a 2,6-trans-substituted tetrahydropyran by selenium-mediated intramolecular cyclization. Moreover, dramatic solvent effects observed in the macrolactonization reaction suggest that hydrogen-bonding effects play a critical role. An improved route to a key intermediate of our synthesis is documented.