Unified Total Synthesis of (−)‐Enigmazole A and (−)‐15‐O‐Methylenigmazole A.

The total synthesis of cytotoxic marine phosphomacrolides, (−)‐enigmazole A and (−)‐15‐O‐methylenigmazole A, is described in detail. The 2,6‐cis‐substituted tetrahydropyran ring was efficiently elaborated by using a tandem olefin cross‐metathesis/intramolecular oxa‐Michael addition reaction. The 18‐membered macrolactone skeleton was forged via a Au‐catalyzed propargylic benzoate rearrangement/macrocyclic ring‐closing metathesis sequence. Late‐stage diversification of a common intermediate enabled unified total synthesis of (−)‐enigmazole A and (−)‐15‐O‐methylenigmazole A. [ABSTRACT FROM AUTHOR]