Synthesis of 16S-Iloprost

Significance

Iloprost is used for the treatment of arterial occlusion and pulmonary arterial hypertension. It is produced as a 1:1 mixture of 16S and 16R diastereoisomers but the 16S diastereoisomer is 20 times more active than the 16R analogue. The present synthesis is the first fully stereo­selective synthesis of the more potent 16S isomer. Noteworthy steps include the asymmetric desymmetrization of the meso-ketone A, the conjugate addition of the alkenylcopper reagent to azoalkene B and the asymmetric Horner-Wads­worth-Emmons reaction to secure the E-trisubstituted alkene (D to E).