Total synthesis of (-)-enigmazole A, a marine macrolide natural product with cytotoxic activity, has been accomplished. The tetrahydropyran moiety was constructed by means of a domino olefin cross-metathesis/intramolecular oxa-Michael addition of a δ-hydroxy olefin. After coupling of advanced intermediates, the macrocycle was formed through gold-catalyzed rearrangement of a propargylic benzoate, followed by ring-closing metathesis of the resultant α,β-unsaturated ketone.
Keywords: macrocycles; metathesis; natural products; rearrangement; total synthesis.
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