Development of the effecient synthetic methods of some pharmeceuticals by using the generalized asymmetric epoxidation

我们对简单烯烃的不对称环氧化反应进行了研究，为药物的合成提供了一种有用的方法，并发现精心设计的（salen）锰（III）配合物是共轭烯烃环氧化反应的有效催化剂。为了开发更有效的催化剂，我们今年研究了使用（salen）锰（III）催化剂的环氧化反应机理，并提出了催化剂的不对称诱导的独特机理：salen催化剂的高不对称诱导主要归因于salen配体的不对称非平面结构。基于这一新的知识，我们可以发现，一个非手性（salen）锰（III）配合物催化环氧化反应的存在下，光学胺在一个对映选择性的方式。虽然目前该反应的对映选择性对于实际应用还不够高，我们还开发了苯乙烯衍生物的不对称氮丙啶化反应和通过（salen）锰（III）修饰的不对称苄基羟基化反应。这些新的反应有望成为合成多种药物的有效工具。

We have studied on asymmetric epoxidation of simple olefins to provide a useful methodology for the synthesis of pharmaceuticals and found that well-designed (salen) manganese (III) complexes are efficient catalysts for epoxidation of conjugated olefins. To develop the more effective catalyst, we examined about the reaction mechanism of epoxidation using a (salen) manganese (III) catalyst this year and could propose a unique mechanism of asymmetric induction by the catalysts : the high asymmetric induction by salen catalyst is mainly attributable to asymmetric non-planar structure of the salen ligand. Based on this new knowledge, we could find that an achiral (salen) manganese (III) complex catalyzes epoxidation in the presence of an optically amine in a enantioselective manner. Although enantioselectivity of the reaction is not high enough for practical use at present, this new methodology using readily available and non-expensive achiral salen catalyst will lead to the development of more economical epoxidation.We also developed asymmetric aziridination of styrane derivatives and asymmetric benzylic hydroxylation by the modification of the (salen) manganese (III) complex we had reported.These new reactions are expected to be efficient tools for the synthesis of wide variety of pharmaceuticals.