Cascade Cyclization Synthesis of Fused Polycyclic Ethers

在本研究项目中，Frank E.埃默里大学的McDonald正在开发结构复杂的海洋天然产品的有效制备方法，例如Brevenal，这是一种无毒的空气传播毒素抑制剂，由包括墨西哥湾在内的热带和亚热带海洋地区的赤潮事件自然产生。 为了减少构建这种结构复杂的化合物所需的大量步骤，研究计划通过利用新的顺序环化策略来化学合成多环醚来解决这一挑战，其中brevenal作为主要目标结构。 这项研究的更广泛的影响包括一个合作练习，其中学生，包括那些在这个项目上工作，提高他们的科学沟通技巧，以更好地向公众解释科学家做什么，为什么他们做的是重要的。学生们就正在进行的或最近完成的研究经验进行简短的演讲，针对不同的观众，包括受过教育的成年非科学家，和小学年龄的孩子，并收到同学们对演讲的反馈。为了有效地制备稠合多环醚天然产物，埃默里大学的小组正在努力利用立体和区域选择性级联成环反应。所提出的工作将稠合多环醚合成的级联环化的范例从狭窄的集中于困难的内模式聚环氧化物环化，转移到其他级联环化方法，包括本项目中的外模式氧杂环化策略。 拟议的工作包括提高科学沟通技能的练习，无论是对学生在这个项目上工作，并为其他学生在化学高级课程。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Prof. Frank E. McDonald of Emory University is developing the efficient preparation of structurally complex marine natural products, exemplified by brevenal, a non-toxic inhibitor of airborne toxins naturally produced by red tide events in tropical and subtropical marine regions, including the Gulf of Mexico. To decrease the large number of steps required to construct such structurally complex compounds, the research plan addresses this challenge by exploiting a new sequential cyclization strategy for the chemical synthesis of polycyclic ethers, with brevenal as the principal target structure. Broader impacts of this research include a collaborative exercise in which students, including those working on this project, improve their scientific communication skills to better explain to the general public what scientists do, and why what they do is important. Students make short presentations on an ongoing or recently completed research experience, directed to diverse audiences, including an educated adult non-scientist, and an elementary school-age child and receive feedback on presentations by peer students.In order to efficiently prepare fused polycyclic ether natural products, the Emory group is working to harness stereo- and regioselective cascades of ring-forming reactions. The proposed work shifts the paradigm of cascade cyclizations for fused polycyclic ether synthesis from a narrow focus on the difficult endo-mode polyepoxide cyclization, to other cascade cyclization approaches including the exo-mode oxacyclization strategy in this project. The proposed work includes exercises in improving scientific communication skills, both for students working on this project and for other students taking advanced coursework in chemistry.