RUI: A Cyclopropane Fragmentation Approach to Heterocycle Synthesis

本项目旨在发展一条统一的合成不同环尺寸和杂原子的杂环化合物的路线。提出的化学依赖于环丙醇的亲核性，未充分利用，但称职的亲核试剂，在原位生成的亚胺或氧物种上环化。这种缩合/重排策略导致环扩张，并保证高水平的立体控制。在氧杂环庚烷体系中进行反应优化后，该杂环形成策略将扩展到四氢吡喃、哌啶和氮杂卓的合成中。该方法的实用性将在spectalinine A的合成和isoarurepinnacin的正式合成中得到展示。在有机和大分子化学项目的RUI奖的支持下，詹姆斯麦迪逊大学化学系的Kevin P. Minbiole教授正在探索一种合成杂环的新方法，杂环是至少包含一个非碳原子的分子环。杂环化合物构成了无数具有生物医学重要性的化合物的骨架。该项目旨在开发一种合成具有不同环尺寸和杂原子的杂环的统一路线。随着新方法的开发，它们的效用将通过它们在代表性天然存在的化合物的合成中的应用来说明。该计划的所有工作将由本科生进行，包括来自研究活动较少的地区大学的学生。

This project aims to develop a unified route to the synthesis of heterocycles with different ring size and heteroatom. The chemistry proposed relies on the nucleophilicity of cyclopropanols, underutilized but competent nucleophiles, cyclizing on an in-situ generated iminum or oxonium species. This condensation/rearrangement strategy results in a ring expansion, and promises high levels of stereocontrol. After reaction optimization in the oxepane system, this heterocycle formation strategy will be extended to the synthesis of tetrahydropyrans, piperidines, and azepines. The utility of this methodology will be showcased in the synthesis of spectalinine A and a formal synthesis of isolaurepinnacin.With the support of this RUI award from the Organic and Macromolecular Chemistry Program, Professor Kevin P. Minbiole, of the Department of Chemistry at James Madison University, is exploring a new approach for the synthesis of heterocycles, molecular rings containing at least one atom that is not carbon. Heterocyclic compounds constitute the backbone of innumerable compounds of biomedical importance. This project aims to develop a unified route to the synthesis of heterocycles with different ring sizes and heteroatoms. As new methodologies are developed, their utility will be illustrated through their application in the synthesis of representative naturally occurring compounds. All work in this program will be carried out by undergraduates, including students from less research-active regional colleges.