RADICAL MEDIATED CYCLIZATION REACTIONS

自由基介导的环化反应

• 批准号: 2178888
• 负责人: KEN S. FELDMAN
• 金额: $ 16.5万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2178888
• 关键词: alcohols; alkenes; antileukemic agent; antineoplastic antibiotics; chemical addition; chemical bond; cyclization; cyclopentane; drug design /synthesis /production; free radicals; oxetane; stereochemistry

Many therapeutically important natural products and pharmaceutical agents can be prepared from functionalized cyclopentane and dioxolane derivatives. The continued development of methodology for the efficient and stereoselective synthesis of these ring systems is proposed. This methodology is based on the free radical mediated addition of functionalized olefins or related species across the carbon-carbon bond of suitably activated vinylcyclopropanes to afford directly the cyclopentane units. Emphasis is placed on enhancing current levels of dia- stereoselectivity and enantioselectivity upon bond formation. Further, the development of novel free radical-based annelation/isomerization reactions for the construction of highly functionalized cyclopentanol species is planned. Finally, diastereoselective remote (Gamma) functionalization of secondary alcohols will be explored. Syntheses of the antitumor antibiotic brefeldin A and The antileukemic agent rocaglamide, which each utilize intramolecular variants of the cyclo- pentannelation process, will be investigated. Successful completion of these syntheses will afford the targets (or analogs) in the most efficient manner to date.

许多具有治疗意义的天然产物和药剂 可以由官能化的环戊烷和二氧戊环衍生物制备。 持续开发高效、高效的方法论 提出了这些环系统的立体选择性合成。 这 方法基于自由基介导的添加 跨碳-碳键的官能化烯烃或相关物质 适当活化的乙烯基环丙烷直接提供环戊烷 单位。 重点是提高当前的糖尿病水平 键形成时的立体选择性和对映选择性。 此外， 新型基于自由基的退火/异构化反应的发展 用于构建高功能化的环戊醇物种是 计划。 最后，非对映选择性远程（Gamma）功能化 将探索仲醇。 抗肿瘤抗生素布雷菲德菌素 A 和抗白血病药物的合成 药物罗卡酰胺，其各自利用环-的分子内变体 五退火工艺，将被研究。 顺利完成 这些合成将以最有效的方式提供目标（或类似物） 迄今为止的方式。