Total Synthesis of (−)-Enigmazole A

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 forged via a gold-catalyzed rearrangement of a propargylic benzoate, followed by a ring-closing metathesis of the resultant α,β-unsaturated ketone.