Enantioselective Total Synthesis of Communesin F

描述(申请人提供)：拟议的工作将使生物碱天然产物(-)-Commesin F的收敛、对映体选择性和仿生合成成为可能。(-)-Commesin F属于一类天然产品，包含结构独特的七环骨架。这一系列天然产品展示了一系列有趣的生物活动。在生物合成的启发下，复杂的异源二聚体的重排应该可以提供Commesin生物碱的核心。我们新开发的异二聚化方法的应用将使我们能够快速获得必要的二聚体。该方法以不对称双氮烯形式的复合胺的逐步结合为中心，然后光排出二氮，以提供异二聚体产品。总而言之，建议的路线将 提供一种快速和收敛的(-)-Commesin F的合成，该合成有可能扩展到Commesin天然产品家族的所有成员。 与公共卫生的相关性：生物活性天然产品继续被用于一些医疗治疗。这些天然产物的有效合成不仅允许它们对各种疾病进行测试，而且还允许合成可能更有效的衍生物。在这里，我们描述了具有不同生物活性的生物碱天然产物家族中的一员--香豆素F的对映选择性合成。建议的路线将利用新开发的通过重氮烯裂解进行异二聚化的方法，以及生物合成启发的重排来提供Commesin核心。

DESCRIPTION (provided by applicant): The proposed work would enable the convergent, enantioselective, and biomimetic synthesis of the alkaloid natural product (-)-communesin F. (-)-Communesin F belongs to a family of natural products containing a structurally unique heptacyclic framework. This family of natural products displays a range of interesting biological activities. A biosynthetically inspired rearrangement of a complex heterodimer should afford the core of the communesin alkaloids. Application of our newly developed method for heterodimerization will allow rapid access to the necessary dimer. The method centers on the stepwise union of complex amines in the form of unsymmetrical diazenes followed by photoexpulsion of dinitrogen to afford the heterodimerized product. In all, the proposed route will afford a rapid and convergent synthesis of (-)- communesin F which potentially could be expanded to all members of the communesin family of natural products. PUBLIC HEALTH RELEVANCE: Biologically active natural products continue to be utilized in a number of medicinal treatments. The efficient synthesis of these natural products allows not only for their testing against various diseases but also allows for the synthesis of potentially more potent derivatives. Here in we describe the purposed enantioselective synthesis of communesin F a member of a family of alkaloid natural products with varying biological activity. The proposed route will take advantage of the newly developed method for heterodimerization via diazene fragmentation as well as a biosynthetically inspired rearrangement to afford the communesin core.