Minimal Peptide Catalysts for Asymmetric Synthesis

本计画旨在设计与开发介导立体选择性反应之胜肽结构与多功能触媒。将合成在由小肽提供的明确定义的结构内并入官能团的催化剂。除了基于机理的设计之外，还将采用基于系统多样性的方法来发现和优化催化剂。本项目的主要目标是通过酰基阴离子中间体的生成，发现新的肽基催化剂用于对映选择性的非极性催化，拓展共催化概念，（涉及不同的肽和氨基酸催化配偶体）在Morita-Baylis-Hillman反应及其相关物的背景下;以及基于新发现的胺催化的丙二烯酸酯-烯酮偶联的新的丙二烯对映选择性反应的发现。这些研究将使肽基催化剂进入轴向手性立体控制领域。有了这个奖项，有机和大分子化学计划正在支持波士顿学院化学系的Scott J.米勒博士的研究。化学合成领域准备为新药物的鉴定和新材料的制备做出巨大贡献。发现产生新结构的高效反应将在这些努力中发挥关键作用。该项目旨在发现新的催化剂，这些催化剂将以高活性和高效率以及环境友好的方式介导化学反应。米勒教授和他的学生们利用了许多酶在实现有效催化时所使用的相同原理，但这样做的分子复杂性只有一小部分。这项工作是在教育阶梯的多个层面上进行协作的环境中进行的，包括来自主要本科院校的本科生的参与。

This project addresses the design and exploitation of peptide architectures and multifunctional catalysts that mediate stereoselective reactions. Catalysts that incorporate functional groups within the well-defined architecture afforded by small peptides will be synthesized. In addition to mechanism-based design, systematic diversity-based approaches will be taken to catalyst discovery and optimization. With an overall focus on enantioselective C-C bond formation reactions, the goals of this project include the discovery of new peptide-based catalysts for enantioselective umpolung catalysis through the generation of formal acyl anion intermediates; the expansion of the cocatalysis concept (involving distinct peptide and amino acid catalytic partners) in the context of the Morita-Baylis-Hillman reaction and its relatives; and the discovery of novel enantioselective reactions of allenes based on a newly discovered amine-catalyzed allenoate-enone coupling. These studies will bring the peptide-based catalysts into the area of axial chirality stereocontrol.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Scott J. Miller of the Department of Chemistry at Boston College. The field of chemical synthesis stands poised to make enormous contributions to the identification of new pharmaceuticals and in the preparation of novel materials. The discovery of highly efficient reactions that generate novel structures will play a critical role in these endeavors. This project is directed at the discovery of new catalysts that will mediate chemical reactions with high activity and efficiency, and in an environmentally benign fashion. Professor Miller and his students utilize many of the same principles that enzymes use in achieving efficient catalysis, but do so with a fraction of the molecular complexity. The work is conducted in an environment that is collaborative at multiple levels of the educational ladder, including the involvement of undergraduate students from primarily undergraduate institutions.