Leveraging Cyclopropanols in Natural Product Synthesis

在化学系化学合成项目的支持下，Wayne州立大学的Jin Cha教授正在开发有机化学或药物化学中使用的重要分子的有效途径。从现成的三元环化合物开始，研究计划以模块化的方式构建复杂的分子，以构建具有理想特性的天然分子。这项提议的工作建立在最初的三元环形成的关键修改上，为新的化学合成铺平道路。这些研究将具有潜在的更广泛的社会效益，因为趋同的、无害环境的和可持续的合成为制药、化学、农业工业和材料科学提供了有利的工具。该项目将为同事提供优秀的培训，从本科研究参与者到博士后研究员，包括那些在STEM（科学、技术、工程和数学）领域历史上代表性不足的群体。在美国韦恩州立大学化学系化学合成项目的支持下，查教授正在研究天然产物的高效合成，特别强调效率和选择性。两个多功能片段的耦合（结合）有助于复杂分子的实际合成。本课题将重点研究环丙醇或相关的钛环丙烷的交叉偶联反应的开发和应用，以开发简洁的合成路线。Cha小组将继续利用环丙醇作为一种独特的非外消旋和具有吸引力的功能化同源烯醇在C-C键形成中的等价物。过渡金属催化的两段交叉偶联反应包括环丙醇的c -酰化、SN2′烷基化、烯化和烷基化。关键合成方法的制备能力将在一系列结构新颖和生物学上重要的天然产物的预测简明全合成中得到强调。这些目标包括虫毒素、生物碱261C、scholarisine A、青蒿素和丝裂霉素c。该奖项反映了美国国家科学基金会的法定使命，并通过基金会的知识价值和更广泛的影响审查标准进行了评估，认为值得支持。

With the support of the Chemical Synthesis program of the Division of Chemistry, Professor Jin Cha of Wayne State University is developing efficient routes to important molecules which are utilized in organic or medicinal chemistry. Starting with readily available three-membered ring compounds, the research plan builds complex molecules in a modular approach to construct naturally occurring molecules endowed with desirable properties. The proposed work builds on a key modification in the initial three-membered ring formation to pave the way for new chemical syntheses. These studies will have potential for broader societal benefits, as convergent, environmentally benign and sustainable syntheses offer enabling tools in pharmaceutical, chemical, agricultural industry, and materials science. This project will provide excellent training for coworkers, from undergraduate research participants to post-doctoral fellows, including those from groups historically underrepresented in STEM (science, technology, engineering and mathematics) fields.With the support of the Chemical Synthesis program of the Division of Chemistry, Professor Cha of Wayne State University is studying an efficient synthesis of natural products with particular emphasis on efficiency and selectivity. Coupling (union) of two polyfunctional fragments lends itself to practical syntheses of complex molecules. The proposed study will focus on the development and application of cross-coupling reactions of cyclopropanols or the related titanacyclopropanes to develop concise synthetic routes. The Cha group will continue to utilize cyclopropanols as a unique family of nonracemic and attractively functionalized homologous enol equivalents in the C–C bond formation. Transition metal-catalyzed cross-coupling reactions of two segments include C-acylation, SN2’ alkylation, alkenylation, and alkynylation of cyclopropanols. The preparative power of the key synthetic methods are to be highlighted in projected concise total syntheses of an array of structurally novel and biologically important natural products. Among these targets are included gephyrotoxin, alkaloid 261C, scholarisine A, artemisinin, and mitomycin C.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.