Total Synthesis of UCS1025A via Tandem Carbonylative Stille Cross Coupling and Diels-Alder Reaction

We report an efficient and convergent strategy for the total synthesis of UCS1025A and its diastereomer tetra-epi-UCS1025A. UCS1025A is a representative member of the naturally occurring pyrrolizidinone polyketides, from which members with potent antibacterial, antifungal, and anticancer activities have been identified. Our approach features a tandem carbonylative Stille cross coupling and Diels-Alder reaction to forge a key C-C bond and build the trans-decalin system. This tandem process utilizes carbon monoxide as a one-carbon linchpin to stitch a vinyl triflate and a vinylstannane together and form the desired enone moiety for the subsequent intramolecular Diels-Alder cyclization. Our synthesis also provides a versatile approach for the synthesis of other related pyrrolizidinone-containing polyketides.