Target-Oriented Synthesis of the Prostacyclin Derivative Beraprost

拟议项目的目的是靶向，对端选择性合成前列环素伯拉前列素，其钠盐已被用作治疗继发性肺动脉高压的药物。因此，该项目具有很高的社会影响，因为到目前为止还没有对映选择性合成的berap前列素。Beraprost是一种具有二氢苯并[b]呋喃基序的三环前环素衍生物，其环成环戊烷环。这个三环主链被合成过程中引入的两个侧链取代。总的来说，苯丙醇有六个立体中心，其中四个在环戊烷环上。提出的合成从两个环状五元环的对映选择性构建开始。合成的关键步骤是先前报道的l -脯氨酸与三氟乙酸二苄胺催化的多米诺醛反应。进一步的分子反合成分析提供了两种可能的合成途径，应该在项目中进行研究。最后，所开发的合成将用于制备进一步的前列环素类似物，以构建该类新的活性物质。

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.