Development of a Concise Stereospecific Strategy for the Total Synthesis of Xestodecalactone A and (S)-Curvularin

Abstract A concise, stereospecific synthesis of the benzannulated macrolactones Xestodecalactone A and (S)-curvularin was achieved using a unified strategy of regioselective epoxide opening, Steglich esterification, and a pivotal intramolecular Friedel–Crafts acylation. The route utilizes 3,5-dimethoxyphenylacetic acid as the common aromatic core, paired with specific chiral epoxides and alkyne synthons: (R)-propylene oxide and propargyl alcohol for Xestodecalactone A, and (S)-propylene oxide and pent-4-yn-1-ol for (S)-curvularin. This modular approach demonstrates a highly efficient general protocol for accessing diverse dihydroxyphenylacetic acid lactones by simply varying the starting building blocks.