Cascade Cyclization Synthesis of Fused Polycyclic Ethers

化学合成项目支持埃默里大学Frank E. McDonald教授的研究，该项目探索以烯丙基氧取代基为立体诱导元素的无环多烯前体的立体和区域选择性外模式环化。该项目是一种新的级联多环化方法的基础，brevenal是一种无毒的brevenal毒素结合抑制剂。授权期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，以及证明双环化和多环形成多环化过程的可行性和普遍性。为了解决有意义的包括本科生研究人员和K-12科学教师等经验不足的研究人员的更广泛影响，McDonald实验室还开发了新的合成路线，用于级联环化过程所需的无环前体，基于合成社区普遍感兴趣的多功能构建块的高效和可扩展的制备。本研究的重点是发现结构复杂的海洋化合物化学合成的新策略。在这一领域取得进展的一个关键障碍是制备具有潜在药用和商业重要性的化合物所需的数十个步骤。McDonald实验室正在通过开发一种新的合成策略来解决这一挑战，该策略可以从相对简单且容易制备的线性前体中，在一次操作中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，如brevenal，它是热带和亚热带海洋地区（包括墨西哥湾）红潮事件自然产生的空气毒素的无毒抑制剂。这项研究的更广泛影响包括本科生和K-12科学教师，通过埃默里大学的几个暑期研究项目。

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.