RUI: Development of Dianionic Enolates for the Stereoselective Synthesis of Natural and Unnatural Amino Acids

美国国家科学基金会化学部的化学合成项目通过该奖项支持了西方学院杰弗里·坎农教授的研究，他与本科生研究人员一起合成了非天然氨基酸。氨基酸是生物系统的基本组成部分之一。坎农教授和他的研究小组正在设计新的策略来合成这些构建块，这些构建块可以提供有用数量的氨基酸，这些氨基酸不易从自然来源中分离出来。此外，由于它们的三维形状或立体化学对其正常功能至关重要，因此本研究致力于控制氨基酸产物中原子的精确排列，从而使产物在生物系统中正常发挥作用。坎农教授和他的研究小组随后将这些结果应用于吲哚嘧啶分子家族的化学合成。吲哚吡啶结构存在于许多生物活性分子中。这种类型的分子作为药物和其他生物制剂有许多应用。更广泛的影响包括新的合成和非天然氨基酸的应用，以及生物活性含氮分子的发展。该项目还为合成化学专业的本科生设立了夏季研究奖学金，重点是为代表性不足的学生提供支持。合成非天然氨基酸有许多限制，特别是那些完全取代的氨基酸。坎农教授和他的学生正在开发重阴离子烯醇酸酯的反应，为非天然氨基酸衍生物和其他合成前体提供现成的立体选择性途径。他的研究小组正在研究使用手性助剂来指导重阴离子烯醇酯反应的立体化学。为了了解这些助剂所提供的控制因素，我们对这些反应进行了实验和计算研究。目标是为氨基酸的合成提供一个强大的和可访问的系统。这些反应在复杂的环境中进行测试，以了解其局限性并激发进一步的反应发展。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With this Award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Jeffrey Cannon at Occidental College who works with undergraduate researchers to synthesize unnatural amino acids. Amino acids are one of the fundamental building-blocks of biological systems. Professor Cannon and his research team are devising new strategies for the synthesis of these building blocks that can provide useful quantities of amino acids that are not readily isolated from natural sources. Furthermore, because their three-dimensional shape or stereochemistry is critical for proper function, this research is working to control the exact arrangement of atoms in the amino acid products so that the products function properly in biological systems. Professor Cannon and his research team then apply these results to the chemical synthesis of a family of molecules known as indolizidines. The indolizidine structure is found in many biologically-active molecules. Molecules of this type have many applications as pharmaceuticals and other biological agents. The broader impacts include new syntheses and applications of unnatural amino acids as well as the development of biologically-active nitrogen-containing molecules. This project also creates summer research fellowships for undergraduates in synthetic chemistry with an emphasis on support for underrepresented students.There are many limitations to the syntheses of unnatural amino acids, especially those that are fully-substituted. Professor Cannon and his students are developing the reactions of dianionic enolates to provide ready stereoselective access to unnatural amino acid derivatives and other synthetic precursors. His research group is investigating the use of a chiral auxiliary to direct the stereochemistry of reactions of dianionic enolates. These reactions are studied experimentally as well as computationally in order to understand the elements of control provided by these auxiliaries. The goal is to provide a robust and accessible system for the synthesis of amino acids. These reactions are tested in complex settings in order to understand their limitations and inspire further reaction development.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.