Cascade Cyclization Synthesis of Fused Polycyclic Ethers

稠合多环醚的级联环化合成

• 批准号: 1151304
• 负责人: Frank McDonald
• 金额: $ 15万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1151304&HistoricalAwards=false
• 关键词: Cascade; Cyclization; Synthesis; Fused; Polycyclic

The Chemical Synthesis Program supports the research of Prof. Frank E. McDonald at Emory University, in a project exploring the stereo- and regioselective exo-mode cyclizations of acyclic polyene precursors bearing allylic oxygen substituents as stereoinduction elements. This project is the basis for a novel cascade polycyclization approach to brevenal, a non-toxic inhibitor of brevetoxin binding. Major objectives for the granting period include uncovering the diastereoselectivities of metal-catalyzed cycloisomerization and halonium-ion mediated cyclization processes, and demonstrating the feasibility and generality of bicyclization and multiple ring-forming polycyclization processes. In addressing the broader impact of meaningful inclusion of less-experienced researchers such as undergraduate researchers and K-12 science teachers, the McDonald laboratory also develops new synthetic routes for the acyclic precursors required for cascade cyclization processes, based on efficient and scalable preparations of multiply-functionalized building blocks of general interest to the synthetic community. This research focuses on discovering new strategies for the chemical synthesis of structurally complex compounds of marine origin. A critical barrier to progress in this field has been the dozens of steps required for preparing compounds of potential medicinal and commercial importance. The McDonald laboratory is addressing this challenge by developing a novel synthetic strategy, to form structurally complex compounds in a single operation, from relatively simple and easily prepared linear precursors. The potential impact of this research includes the efficient preparation of relatively complex compounds such as brevenal, which is a non-toxic inhibitor of airborne toxins naturally produced by red tide events in tropical and subtropical marine regions, including the Gulf of Mexico. Broader impacts of this research feature inclusion of undergraduate students and K-12 science teachers through several summer research programs at Emory.

化学合成计划支持埃默里大学 Frank E. McDonald 教授的研究，该项目探索带有烯丙基氧取代基作为立体诱导元件的无环多烯前体的立体和区域选择性外模式环化。 该项目是针对布雷诺（brevenal）的新型级联多环化方法的基础，布雷诺是一种无毒的短链毒素结合抑制剂。 授权期间的主要目标包括揭示金属催化的环异构化和卤离子介导的环化过程的非对映选择性，并证明双环化和多重成环多环化过程的可行性和普遍性。 为了解决有意义地纳入本科研究人员和 K-12 科学教师等经验不足的研究人员的更广泛影响，麦克唐纳实验室还基于合成界普遍感兴趣的多功能化构建块的高效和可扩展的制备，为级联环化过程所需的无环前体开发了新的合成路线。这项研究的重点是发现海洋来源的结构复杂化合物的化学合成新策略。 该领域取得进展的一个关键障碍是制备具有潜在医学和商业重要性的化合物所需的数十个步骤。 麦克唐纳实验室正在通过开发一种新颖的合成策略来应对这一挑战，通过单一操作从相对简单且易于制备的线性前体形成结构复杂的化合物。 这项研究的潜在影响包括有效制备相对复杂的化合物，例如布雷纳尔，它是一种无毒抑制剂，可抑制热带和亚热带海洋地区（包括墨西哥湾）赤潮事件自然产生的空气毒素。 这项研究的更广泛影响包括通过埃默里大学的几个暑期研究项目纳入本科生和 K-12 科学教师。