Synthesis Driven by Release of Ring Strain

在这个由化学系化学合成计划资助的项目中，韦恩州立大学化学系的查教授正在研究几种在有机和药物化学中有实用价值的分子构建块的有效制备。这项研究项目从容易获得的环丙醇开始：三元环化合物，像弹簧一样拉伸，据说有环张力。打开三元环的反应通过释放这种环张力来驱动完成。CHA实验室对这些环丙醇的制备进行了显著改进。他们正在开发环丙醇的新反应，以构建更复杂的分子，这些分子可能具有有用的药用特性。这个项目是年轻科学家从本科生研究人员到博士后研究员学习化学的极好的培训场所。该项目的具体目标包括设计新的化学反应，促进重要结构基元或天然产品的简明和环境友好的合成。重点是高效率和收敛的使用片段耦合策略，其中两个大片段连接在合成的后期阶段。蛇床子酮和生物碱261C的简明全合成正在进行中。这些合成突出了新开发的合成方法的制备能力。松香酮和生物碱261C都是稀有的天然产物，需要进行化学合成来评价它们的生物活性。通过参与该项目，学生和博士后将接受有机方法开发、有机金属化学和天然产物合成方面的培训。他们已经为化学职业做好了充分的准备。

In this project, funded by the Chemical Synthesis Program of the Chemistry Division, Professor Cha of the Department of Chemistry at Wayne State University is investigating an efficient preparation of several molecular building blocks that have utility in organic and medicinal chemistry. The research project begins with readily available cyclopropanols: three-membered ring compounds that are tensioned like a spring and said to have ring strain. Reactions that open the three-membered rings are driven to completion by releasing this ring strain. The Cha laboratory developed a significantly improved preparation of these cyclopropanols. They are developing new reactions of cyclopropanols to build more complex molecules that may have useful medicinal properties. This project is an excellent training ground for young scientists, from undergraduate researchers to post-doctoral fellows, to learn about chemistry. The specific goals for the project include the design of new chemical reactions that facilitate concise and environmentally benign syntheses of important structural motifs or natural products. Emphasis is placed on high efficiency and convergence by use of segment coupling strategies, in which two large fragments are linked at a late stage in the synthesis. Concise total syntheses of suberosenone and alkaloid 261C are underway. These syntheses highlight the preparative power of the newly developed synthetic methods. Suberosenone and alkaloid 261C are both scarce natural products, and chemical syntheses are necessary to evaluate their biological activity. Through participation in this project, students and postdocs are trained in organic methods development, organometallic chemistry and natural product synthesis. They are well prepared for careers in chemistry.