Renaissance of the truce-smiles rearrangement

化学家通过化学合成的过程制造聚合物和药品等新物质。一个定义了化学反应的“工具箱”控制着可用的起始化学物质可以制造出什么样的产品。化学家手中最有用的反应（“工具”）是那些最容易理解的反应。对化学反应进行彻底调查以获得理解，包括在各种条件下对各种起始化学品进行反应测试，并分析所产生的化学品。我建议研究一种被称为休战-微笑重排的反应，这种反应在20世纪50年代首次被报道，但此后基本上没有被探索过。由于缺乏研究，对休战-微笑重排仍有许多未知或不了解的地方，因此该反应尚未达到“化学工具”的地位。我的研究计划的目标是阐明这个反应，并把它提升到一个可靠的、有用的合成反应的地位。这将通过检查用于进行反应的条件并优化它们来实现，以最大限度地提高能源效率，最大限度地减少浪费和环境影响。将调查反应的范围，以确定其普遍性和对起始化学品的容忍限度。改进后的休战-微笑重排的有用性将通过将该反应应用于化学合成中的一些挑战以及将作为药物进行测试的化学品库的制备来证明。从长远来看，该反应将用于合成小分子文库，这些小分子将被筛选为选择性半胱氨酸蛋白酶抑制剂。这可能会导致新的抗癌疗法的发展。

Chemists fabricate new substances such as polymers and pharmaceuticals through the process of chemical synthesis. A "toolbox" of defined chemical reactions controls what products can be made from available starting chemicals. The most useful reactions ("tools") at a chemist's disposal are those that are best understood. Thorough investigation of a chemical reaction to gain understanding involves testing the reaction on a variety of starting chemicals under a variety of conditions and analyzing the chemicals produced. I propose to investigate a reaction known as the Truce-Smiles rearrangement that was first reported in the 1950s but has been largely unexplored since. This reaction has not achieved the status of "chemical tool" because there remains a lot that is unknown or not understood about the Truce-Smiles rearrangement due to lack of investigation. The goal of my research program is to illuminate this reaction and elevate it to the position of a reliable, useful synthetic reaction. This will be achieved by examining the conditions that are used to conduct the reaction and optimizing them to maximize energy efficiency and minimize waste and environmental impact. The scope of the reaction will be investigated to determine its generality and the limits of its tolerance for starting chemicals. The usefulness of the improved Truce-Smiles rearrangement will then be demonstrated by applying the reaction to some challenges in chemical synthesis as well as to the preparation of a library of chemicals that will be tested as pharmaceuticals. In the long term, this reaction will be used to synthesize a library of small molecules that will be screened as selective cysteine protease inhibitors. This could lead to the development of new anticancer therapeutics.