Semi-Synthesis of (+)-Digitoxigenin: Selective Bromination for Construction of the Key Intermediate

Abstract A concise and scalable semi-synthesis of (+)-digitoxigenin (1) has been accomplished in nine linear steps. This route features the construction of the C(15)=C(16) double bond in intermediate 6 via selective C16 bromination followed by elimination. Subsequesntly, a single-step SeO2 oxidation directly installed the C14-β-hydroxyl group, producing 7. This strategy avoids precious metals, greatly reduces synthesis costs, and can be extended to the synthesis of related cardiotonic steroids.