Total Synthesis of Marinomycin A Based on a Direct Dimerization Strategy

The asymmetric total synthesis of (+)‐marinomycin A, a 44‐membered macrodiolide antitumor agent and antibiotic isolated from a marine actinomycete, Marinispora strain CNQ‐140, is reported. The key features of the synthesis include the highly convergent stereocontrolled construction of the monomeric hydroxy salicylate starting from asymmetric epoxidation of the σ‐symmetrical dialkenyl carbinol, and an unprecedented direct dimerization through NaHMDS‐promoted double transesterification.