Seeking Equality from an Asymmetric System: The Convergent Total Synthesis of Prostacyclin Drug (±)-Beraprost Sodium

(±)-Beraprost sodium is an oral prostacyclin drug used to treat pulmonary arterial hypertension (PAH). It exists as a mixture of two C-4 diastereomers in a ratio of approximately 1:1, which presents significant challenges for process development. Herein, we report a novel and convergent total synthesis of (±)-beraprost sodium that enables precise control over the C-4 stereochemistry. This synthesis features key transformations including the Mitsunobu reaction, ring-closing metathesis, intramolecular Heck reaction, and cross-electrophile coupling, providing an efficient route to the target compound. Furthermore, systematic investigation into Horner-Wadsworth-Emmons olefination and ketone reduction has yielded a robust method for achieving the desired 1:1 diastereomeric ratio at C-4 from the asymmetric skeleton.