手性高价碘试剂催化的不对称多烯环化反应的研究

Steroids and terpenoids are core structures found in many natural products and pharmaceuticals. The development of enantioselective synthetic strategy of those compounds is of great significant. The cation initiated enantioselective polyene cyclization is a highly efficient approach to the enantioenriched steroids and terpenoids. In this proposal, the oxidation of phenol or aniline derivatives mediated by chiral hypervalent iodine reagents will be employed to initiate enantioselective polyene cyclization reaction to provide facile access to optically pure steroid and terpenoid derivatives. 1) Six classes polyene substrates will be designed and prepared to synthesize fused or spiro polycyclic products by adjusting the position of –OH on phenol or -NH2 on aniline derivatives. 2) Two classes of chiral hypervalent iodine reagents will be designed and synthesized by introducing chiral groups to the ortho position of iodine. 3) The total synthesis of 1-2 optically pure natural products will be accomplished by employing the chiral hypervalent iodine reagents catalyzed enantioselective polyene cyclization. Unlike previous electrophile initiated polyene cyclizaiton reactions, the chiral hypervalent iodine reagents not only initiates the polyene cyclization via oxidation but also controls the stereoselectivity of the reaction.

萜和甾族类化合物广泛存在于天然产物及药物分子当中，因此合成此类化合物具有重要的应用价值。不对称多烯环化反应是构建光学纯萜和甾族类化合物的有效途径。本课题拟通过手性高价碘试剂氧化酚或芳香胺产生碳正离子来诱发不对称多烯环化反应，从而实现结构多样的光学纯萜和甾体衍生物的不对称合成。在本课题中：1) 我们将设计合成六类不同骨架的多烯底物，通过调整酚羟基（氨基）在环上的位置，来合成光学纯螺环或并环的萜和甾族衍生物。2）通过在碘代芳烃碘原子的邻位引入手性基团，设计合成两类新型手性高价碘试剂，并将其用于不对称多烯环化反应中。3) 利用手性高价碘试剂催化的不对称多烯环化反应完成1-2个天然产物的全合成。该方法首次通过高价碘氧化的策略产生碳正离子来引发多烯环化反应，利用高价碘上的手性环境来控制多烯环化的立体选择性。