Asymmetric induction and desymmetrization with organometallic reagents

新的不对称反应和去对称化方法被应用于生物活性前列腺素衍生物如前列环素（PGI2）的合成路线，有望成为抗血小板药物。首先，研究了双（硼氧苯氧基）环戊烯衍生物与格氏试剂在金属卤素交换和随后的环化反应中SN2'的反应，得到了前体环素。以旋光性环戊二醇衍生物为原料，采用非对称工艺合成了所需化合物的真实样品。其次，用手性钯催化剂对中二乙酰氧基环戊烯进行了对映选择性不对称环化反应，得到了所需的前体环化产物，收率在95%以上。最后将上述工艺应用于旋光性前列环素、手性前列环素。此外，还通过几种新的途径合成了非手性苯丙孕酮。

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.