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物等新物质。一个明确的化学反应“工具箱”控制着可以从可用的起始化学品中制造出什么产品。对于化学家来说，最有用的反应(“工具”)是那些最容易理解的反应。彻底调查化学反应以了解情况，包括测试各种起始化学品在各种条件下的反应，并分析产生的化学品。我提议调查一种被称为休战-微笑重组的反应，这种反应最初是在20世纪50年代报道的，但自那以来基本上没有人研究过。由于缺乏调查，关于休战-斯迈尔斯重排仍有许多未知或不了解的情况，因此这一反应并未达到“化学工具”的状态。我的研究计划的目标是阐明这一反应，并将其提升到可靠、有用的合成反应的位置。这将通过检查进行反应的条件并对其进行优化来实现，以最大限度地提高能源效率，最大限度地减少浪费和对环境的影响。将对反应的范围进行调查，以确定其普遍性和对起始化学品的耐受限度。改进的休战-微笑重排的用处随后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药库的制备来证明。从长远来看，这一反应将被用于合成一个小分子文库，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开发。

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.