A GC-MS system to accelerate de-carboxylative method development

这项研究的重点是发现产生碳-碳键的新方法，这是合成有机化学和药物化学中的一项重要变革。这些键历来是通过交叉偶联反应制备的，即在钯催化剂加速的反应中，两个伙伴分子各自具有不同的官能团。在我的团队中开发的程序使用了羧酸来代替通常用来实现这种转变的金属。这是有利的，因为它避免了耦合伙伴的预功能化的需要。此外，反应的主要副产品二氧化碳作为反应的驱动力，显著减少了金属杂质的生成，从而简化了最终的提纯。这项提案中概述的研究需要GC-MS，这是本赠款所要求的设备。GC-MS是鉴定和表征小分子的领先技术。这一仪器将使我们能够在这一发现的基础上，探索利用这种反应性的新方法。在这项研究计划中，将致力于开发具有更高钯效率的新型催化剂，将杂芳酸扩展到新的羧酸，并使用也可以进行这种反应的酸替代品。这些努力将通过减少发现新药所需的时间和通过提高制剂的效率来降低药品成本，从而对制药业产生影响。

The research focuses on the discovery of new methods to create carbon-carbon bonds, which is a vital transformation in both synthetic organic and medicinal chemistry. These bonds have historically been prepared by cross-coupling reactions whereby two partner molecules, each with a different functional group, in a reaction accelerated by a palladium catalyst. The procedure developed in my group employs carboxylic acids in place of the metal which is typically employed to achieve this transformation. This is advantageous since it circumvents the need for the pre-functionalization of the coupling partner. Additionally, the main by-product of the reaction, carbon dioxide, acts as a driving force for the reaction and significantly reduces the amount of metal-based impurities generated, which simplifies final purification. The research outlined in this proposal requires a GC-MS, which is the equipment requested in this grant. GC-MS is a leading technique for the identification and characterization of small molecules. This instrument will allow us to build on this finding and explore novel ways to utilize this reactivity. In this research program, efforts will focus on the development of novel catalysts with increased palladium efficiency, extension beyond heteroaromatic carboxylic acids to new carboxylic acids and the employment of acid surrogates which can also undergo this type of reactivity. These efforts will have an impact on the pharmaceutical industry by both reducing the time required to discover new drugs and reducing drug costs by increasing the effieciency of their preparation.