Stereochemical Determination of the Leupyrrins and Total Synthesis of Leupyrrin A_1

摘要

The stereochemical determination of the potent antifungal agents leupyrrin A_1 and B_1 and the total synthesis of leupyrrin A_1 are reported. The relative and absolute configuration was determined by a combination of high field NMR studies, molecular modeling, and chemical derivatization. The expedient total synthesis involves a one-pot sequential Zr-mediated oxidative diyne-cyclization/regioselective opening sequence for preparation of the unique dihydrofuran ring, a highly stereoselective one-pot approach to the butyrolactone, a challenging sp~2-sp~3 Suzuki coupling and a high-yielding Shiina macrolactonization.