Stereochemical determination of the leupyrrins and total synthesis of leupyrrin A1.

The stereochemical determination of the potent antifungal agents leupyrrin A1 and B1 and the total synthesis of leupyrrin A1 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.