Leveraging Cyclopropanols in Natural Product Synthesis

州立大学韦恩的金查教授在化学系化学合成项目的支持下，正在开发用于有机或药物化学的重要分子的有效路线。 从容易获得的三元环化合物开始，研究计划以模块化方法构建复杂分子，以构建具有所需特性的天然分子。 拟议的工作建立在初始三元环形成的关键修饰上，为新的化学合成铺平道路。 这些研究将有可能带来更广泛的社会效益，因为趋同的、环境友好的和可持续的合成为制药、化学、农业和材料科学提供了有利的工具。 该项目将为同事提供出色的培训，从本科研究参与者到博士后研究员，包括那些来自STEM历史上代表性不足的群体的人（科学，技术，工程和数学）领域。在化学系化学合成计划的支持下，韦恩州立大学的查教授正在研究一种天然产物的高效合成方法，特别强调效率和选择性。 两个多官能片段的偶联（结合）有助于复杂分子的实际合成。 本研究将着重于环丙醇或相关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组将继续利用环丙醇作为独特的非外消旋和有吸引力的官能化同源烯醇等价物家族在C-C键形成。 过渡金属催化的两个链段的交叉偶联反应包括环丙醇的C-酰化、SN 2 '烷基化、烯基化和炔基化。 关键合成方法的制备能力将在一系列结构新颖且具有生物学重要性的天然产物的预计简明全合成中得到强调。 这些目标包括gephyrotoxin，生物碱261 C，青蒿素A，青蒿素和丝裂霉素C。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估。

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.