Total Syntheses of Two Classes of Polyketide Natural Products Lyngbyaloside C and Ambruticin J: Structural Verification and Application of Methodologies

Total syntheses of two classes of polyketides were completed. In the first project, we accomplished a structural reassignment of lyngbyaloside C via total syntheses of the nominal structure and two diastereomers. The longest linear synthetic sequence is 20 steps from readily accessible aldehyde in overall yield 3.4%. This scalable and robust synthetic route features the formation of a tertiary ester and the THP moiety via a one-pot intramolecular ketene esterification. In addition, we applied a regioselective ether transfer reaction in the synthesis of the tertiary alcohol and developed a practical method to synthesize the Z halo-diene. In the second project, we developed a convergent synthetic route toward ambruticin J, which is highlighted a Suzuki-Miyaura cross coupling and Julia-Kocieński olefination. As a highlight of the sequence, we demonstrated a robust synthetic route toward the requisite trisubstituted cyclopropane moiety using cyclopropanation methodology previously developed in our laboratory.