Natural product Synthesis by Rh Catalyzed {2+2+2} Cycloadditions

描述（由申请人提供）：该项目在有机合成方法学方面的广泛，长期目标是开发一种快速，有效和对映体选择性的方法来组装生物相关的含有吲哚里西啶和喹里西啶的天然产物。具体而言，拟议的研究旨在扩展铑催化的[2+2+2]环加成的烯基异氰酸酯与外源性炔，包括官能化的，高反应性的环炔。我们计划将新扩展的方法应用于复杂天然产物的合成：阿可斯明和dasycarpumine。这些二氮金刚烷生物碱已被用作民间药物，用于治疗包括梅毒和疟疾在内的许多疾病。此外，已证明阿科斯明通过增加胰岛素分泌有效治疗大鼠糖尿病。我们选择合成这些生物碱的原因有两个。首先，二氮杂金刚烷骨架构成了独特的合成挑战，其次，将我们的方法应用于这些化合物的合成将突出其实用性，同时将其范围扩展到目前的状态之外。总之，这些化合物的合成将|这将有助于开发治疗糖尿病、梅毒和疟疾的新药。

DESCRIPTION (provided by applicant): The broad, long-term objective of this project in synthetic organic methodology is to develop a rapid, efficient, and enantioselective means of assembling biologically relevant indolizidine and quinolizidine containing natural products. Specifically the proposed research aims to extend the rhodium catalyzed [2+2+2] cycloaddition of alkenyl isocyanates with exogenous alkynes to include functionalized, highly reactive cycloalkynes. We plan to apply the newly expanded methodology to the synthesis of complex natural products: acosmine and dasycarpumine. These diazadamantane alkaloids have been used as folk medicines for the treatment of a number of ailments including syphilis and malaria. Additionally, acosmine has been shown to be effective in the treatment of diabetes in rats by increasing insulin secretion. The reasons we have chosen to pursue the synthesis of these alkaloids are twofold. First, the diazadamantane skeleton poses unique synthetic challenges, and second, the application of our methodology to the synthesis of these compounds would highlight its utility while expanding its scope beyond its current state. Ir all, the synthesis of these compounds wou|d be of benefit to the development of new drugs that could be effective in the treatment of diabetes, syphilis, and malaria.