Target-Oriented Synthesis of the Prostacyclin Derivative Beraprost

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The aim of the proposed project is the target-oriented, enantioselective synthesis of the prostacyclin beraprost, whose sodium salt is already used as a drug to treat secondary pulmonary hypertension. Therefore, this project has a high societal impact since there is no enantioselective synthesis of beraprost so far.Beraprost is a tricyclic prostacyclin derivative with a dihydrobenzo[b]furan motif, which is annulated to a cyclopentane ring. This tricyclic backbone is substituted with two side-chains, which are introduced during the synthesis. Altogether, beraprost has six stereogenic centers, whereof four are present at the cyclopentane ring.The proposed synthesis starts with the enantioselective construction of the two annulated five-membered rings. The key step of the synthesis is the L-proline and dibenzylammonium trifluoroacetate catalyzed domino aldol reaction reported previously. Further retrosynthetic analysis of the molecule provides two possible synthetic pathways, which should be investigated during the project. Finally, the developed synthesis will be applied in the preparation of further prostacyclin analogues for the construction of new, active substances of this class.