Approaches to Improved Synthesis Design: Mechanistic and Synthetic Studies on New Annelation Methods

NSF化学部的化学合成计划支持斯坦福大学化学系保罗·温德教授的项目。温德教授研究有机分子合成的新反应、试剂、催化剂和策略的设计和开发。具体地说，这些反应将较小的分子连接成包含许多碳原子环的更复杂的结构。这些活动创造了新的知识，告诉我们如何制定制造分子的战略，并了解分子形成的化学步骤。这项研究为诊断学、治疗学和材料科学的长期影响奠定了基础。研究生科研训练在学生成长为科学家的过程中起着不可或缺的作用。温德教授培训未来的科学家、工人和教育工作者，他们将继续解决通过化学科学可以解决的环境、经济和健康问题。温德教授从事几个项目，通过创造新的反应、试剂和催化剂，并通过它们在感兴趣的分子的步骤经济合成中的使用，开发关于键形成的新方法。首先，我们研究了一类新的试剂(异丁烯等效物)，并提出了它们在合成激酶抑制剂中的应用。这个项目介绍了一种构建多环的新方法，并说明了这种方法在访问抑制激酶活性的分子方面的价值。第二个项目是使用烯酮类化合物构建功能化的七元环，并将其用于合成托烷生物碱，这些分子具有生物活性。第三个项目开发了四亚甲基乙烷的等价物，这是一种试剂，可以实现合成的许多基本构件的分步经济合成。这项研究与一系列新的溶剂变色染料的合成有关，这些染料可以感觉到它们的分子环境，并通过其荧光的变化来光学“报告”。最后，该项目还寻求开发可在水中运行的新催化剂，这是一种对环境有吸引力的合成溶剂，也是研究生物体系中催化作用的必要溶剂。这些催化剂可以通过催化释放小分子传感器和药物来靶向细胞和器官。这些项目提供了一个全面的培训计划，让学生接触到化学结构、机理和合成的基础知识，同时创造出新的知识，为具有社会价值的应用提供联系。PI和他的同事积极参与创建新的课程、网站和面向高中生的推广活动，这些活动共同利用了本项目中提出的研究。

The Chemical Synthesis Program of the NSF Chemistry Division supports the project by Professor Paul Wender in the Department of Chemistry at Stanford University. Professor Wender studies the design and development of new reactions, reagents, catalysts and strategies for the synthesis of organic molecules. Specifically, the reactions connect smaller molecules into more complex structures that contain many rings of carbon atoms. These activities create new knowledge that informs how we strategize about making molecules and understand the chemical steps through which the molecules are formed. The research lays the foundation for longer-term impacts in diagnostics, therapeutics, and materials science. Graduate student research training performs an indispensable role in the growth of students into scientists. Professor Wender trains future scientists, workers and educators, who will go on to address environmental, economic and health problems that are addressable through chemical science.Professor Wender pursues several projects to develop new ways of thinking about bond formation through the creation of new reactions, reagents and catalysts and through their use in the step-economical synthesis of molecules of interest. In the first, a new class of reagents (cumulene equivalents) is studied and their use in the synthesis of kinase inhibitors is proposed. This project introduces a new way to construct polycycles and illustrates the value of this route in accessing molecules that inhibit the activity of kinases. The second project is directed at the use of ketene equivalents in the construction of functionalized seven-membered rings and their use in the synthesis of tropane alkaloids, molecules of interest due to their biological activity. The third project develops tetramethylene ethane equivalents, which are reagents that enable step economical synthesis of numerous basic building blocks of synthesis. This study is coupled to the synthesis of a new family of solvochromatic dyes, agents that can sense their molecular environment and "report" optically through changes in their fluorescence. Finally, the project also seeks to develop new catalysts that would operate in water, an environmentally attractive solvent for synthesis and a necessary solvent for studies of catalysis in biological systems. These catalysts could be used to target cells and organs by enabling the catalytic release of small molecule sensors and drugs. These projects provide an comprehensive training program, exposing students to the fundamentals of chemical structure, mechanism and synthesis, while at the same time creating new knowledge that provides connections to applications of societal value. The PI and his coworkers are actively involved in the creation of new courses, web sites, and outreach to high school students that collectively draw on the research proposed in this project.