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

Rh 催化 {2 2 2} 环加成合成天然产物

• 批准号: 8137148
• 负责人: Derek M. Dalton
• 金额: $ 3.04万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8137148
• 关键词: Alkaloids; Alkynes; Biological Factors; Complex; Cyclic Acetylenes; Development; Diabetes Mellitus; Folk Medicine; Isocyanates; Malaria; Methodology; Nitrogen; Pharmaceutical Preparations; Rattus; Research; Rhodium; Skeleton; Syphilis; cycloaddition; insulin secretion

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.

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、有效和对映选择性的方法来组装含有生物学相关的吲哚里西啶和喹里西啶的天然产物。具体来说，拟议的研究旨在扩展铑催化的烯基异氰酸酯与外源炔的[2+2+2]环加成反应，以包括官能化的高反应性环炔。我们计划将新扩展的方法应用于复杂天然产物的合成：acosmine 和 dasycarpumine。这些二氮杂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多种疾病。此外，acosmine 已被证明可以通过增加胰岛素分泌来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，二氮杂金刚烷骨架提出了独特的合成挑战，其次，将我们的方法应用于这些化合物的合成将突出其效用，同时将其范围扩大到超出目前的状态。总之，这些化合物的合成将有利于开发可有效治疗糖尿病、梅毒和疟疾的新药。