Synthesis of Alfaprostol and PGF_2α through 1,4-Addition of an Alkyne to an Enal Intermediate as the Key Step

The veterinary drug Alfaprostol and prostaglandin PGF_2α have been synthesized in just nine steps. The strategy involved the conjugate addition of an alkyne to a bicyclic enal, available in three steps by a proline-catalyzed aldol reaction of succinaldehyde. In the case of Alfaprostol, this resulted in the shortest synthesis reported to date. For PGF_2α, this approach improved our previous route by making the 1,4-addition and ozonolysis more operationally simple