Renaissance of the truce-smiles rearrangement

休战微笑重组的复兴

• 批准号: 402608-2011
• 负责人: Wood, Tabitha
• 金额: $ 2.04万
• 依托单位: University of Winnipeg
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=529635
• 关键词: Renaissance; truce; smiles; rearrangement

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.

化学家通过化学合成过程制造新物质，如聚合物和药物。一个定义了化学反应的“工具箱”控制着从可用的起始化学品可以制造出什么样的产品。在化学家的处置最有用的反应（“工具”）是那些最好的理解。彻底研究化学反应以获得理解包括在各种条件下测试各种起始化学品的反应并分析产生的化学品。我建议研究一种被称为“Truce-Smiles重排”的反应，该反应于20世纪50年代首次报道，但此后基本上未被探索。该反应尚未达到“化学工具”的地位，因为由于缺乏研究，对Truce-Smiles重排仍有许多未知或不了解。我的研究计划的目标是阐明这种反应，并将其提升到可靠，有用的合成反应的位置。这将通过检查用于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并最大限度地减少废物和环境影响。将研究反应的范围，以确定其一般性及其对起始化学品的耐受限度。改进的Truce-Smiles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制备将作为药物进行测试的化学品库来证明。从长远来看，这种反应将用于合成一个小分子库，这些小分子将被筛选为选择性半胱氨酸蛋白酶抑制剂。这可能导致新的抗癌疗法的发展。