Total Synthesis of Chloriolin B and Chloriolin C

Chloriolin B 和 Chloriolin C 的全合成

• 批准号: 6405094
• 负责人: Joseph M Ready
• 金额: $ 3.33万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6405094
• 关键词: alkenes; biological products; chemical addition; chemical synthesis; cyclopentane; postdoctoral investigator; stereochemistry

Cyclopentanoid natural products display a wide variety of biological activities, and exhibit diverse and complicated architectures. Total synthesis provides the most efficient vehicle for the examination of these molecules' biological effects. Access to natural products and natural product-like compounds also offers a powerful tool for the elucidation and study of the affected biochemical pathways. Chloriolins B and C are highly oxygenated, chlorinated, linearly fused triquinane natural products recently isolated from an unidentified fungus taken from the Indo-Pacific sponge Jaspis aff. johnstoni. This proposal describes the enantioselective total synthesis of these novel molecules. The proposed synthesis involves the development of the asymmetric trimethylenemethane cycloaddition with activated olefins, and its use in establishing the cis-fused BC ring system. A proposed diastereoselective [3+2] cycloaddition will construct the A ring, and will set the stereochemistry at the AB ring fusion. Successful completion of the total synthesis will constitute the first total synthesis of Chloriolins B and C. This project will also introduce a new method for the asymmetric enantioselective synthesis of five-membered rings and demonstrate its usefulness in complex molecule synthesis.

环戊酸天然产品展示了各种各样的生物学活动，并展示了各种各样且复杂的体系结构。总合成为检查这些分子的生物学作用提供了最有效的载体。使用天然产品和类似天然产品的化合物还为阐明和研究受影响的生化途径提供了强大的工具。氯醇蛋白B和C是高度氧化的，氯化的，线性融合的三喹烷天然产物，该产物最近从从印度太平洋海绵Jaspis AFF中获得的未鉴定真菌分离出来。约翰斯托尼。该建议描述了这些新分子的对映选择性的总合成。提出的合成涉及使用活化烯烃的不对称三甲基甲烷环烷环加成的开发，及其在建立顺式融合的BC环系统中的使用。提出的非对映选择[3+2]环加成将构建A环，并将立体化学设置为AB环融合。成功完成总合成将构成氯醇蛋白B和C的第一个总合成。该项目还将引入一种新方法，用于对五元环的不对称对映选择性合成，并证明其在复杂分子合成中的有用性。