Asymmetric induction and desymmetrization with organometallic reagents

新型的不对称反应和去对称化方法已被应用于前列环素（PGI 2）等具有生物活性的前列腺素衍生物的合成中，该衍生物有望成为抗血小板药物。首先，研究了双（硼苯氧基）环戊烯衍生物与格氏试剂在金属-卤素交换中的SN 2 '反应，然后环化得到前列环素的前体。以旋光环戊二醇衍生物为原料，通过去对称法合成了目标化合物的真实样品。第二步，在手性钯催化剂作用下，内消旋二乙酰氧基环戊烯进行不对称环化反应，得到了95%ee以上的环化前体，收率较高。最后，将上述方法应用于光学活性前列环素、手性贝前列素。此外，非手性贝前列素也通过新的几条路线合成。

New asymmetric reaction and desymmetrization method have been applied in synthetic routes for bioactive prostaglandin derivative such as prostacyclin (PGI2), which is expected as an anti-platelet drugs. First, bis (boromophenoxy) cyclopentene derivatives were examined to SN2' reaction with Grignard reagents in metal-halogen exchange and subsequent cyclization to give a precursor of prostacyclin. An authentic sample of desired compound was synthesized from optically active cycopentanediol derivative by the desymmetric process. Second, meso-diacetoxy-cyclopentene was subjected to enantioselective desymmetric cyclization with chiral palladium catalyst to give the desired cyclization product as a precorsor in over 95% ee in high yield. Finally, above process was applied for optically active prostacycline, chiral Beraprost. In addition, non chiral Beraprost was also synthesized via new several routes.