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 sigma-symmetrical dialkenyl carbinol, and an unprecedented direct dimerization through NaHMDS-promoted double transesterification.