NEW CATALYTIC AND ENANTIOSELECTIVE REACTIONS

拟议的研究项目的主要目标是开发两个新的 不对称催化碳-碳键形成过程。整体而言 目标是增加高效和 对人体重要分子的对映选择性构筑 医疗保健。具有催化作用的反应，以突出的方式进行 高效率和使用廉价材料的选择性可以 极大地缩短了从 治疗候选药物及其大规模制剂和市场推广。 在这方面，新型不对称催化剂的用途 转型将以高效和选择性突出显示 几种重要医药制剂的合成。 要探索的第一个反应是不对称加成 三甲基硅氰化物到环氧化物。初步结果显示， 这一新转型的可行性。后续研究将 通过方便而又系统的修改来优化流程 新型催化体系的肽基配体结构研究进展 更好地从机理上理解反应，并应用这一点 朝着合成各种抗艾滋病毒药物的方向转化。 同样，在亚胺中添加三甲基硅氰化物(Strecker 反应)将发展成一般的催化不对称 转型。再一次，反应的范围将被描绘为 含有配位于多肽配体的金属的催化剂。反应 将对重要分子的机理进行探索和应用 将会被证明。 这两个待开发的反应都将使用路易斯酸性金属 用手性多肽配体作为催化剂进行修饰。的 特别重要的是新催化剂可以达到的速度 准备和优化。这一独特而有用的功能是直接 氨基酸作为配体的手性构筑基团的结果 系统。由于氨基酸是现成的，所以合成多肽 同时计算出了溶液和固相两种状态 多配体结构的制备相对简单。 可以为两者准备和筛选的大量配体 系统的反应性和选择性允许快速 最佳催化体系的选择。

The primary goal of the proposed research project is to develop two new asymmetric catalytic carbon-carbon bond forming processes. The overall objective is to increase the opportunities for efficient and enantioselective construction of molecules important to human healthcare. Reactions that are catalytic, that proceed with outstanding selectivity, that are efficient and use inexpensive materials can dramatically diminish the time span between the conception of a therapeutic candidate and its large scale preparation and marketing. In this regard, the utility of the new asymmetric catalytic transformations will be highlighted with efficient and selective synthesis of several medicinally important agents. The first reaction to be explored is the asymmetric addition of trimethylsilylcyanide to epoxides. Preliminary results have shown the feasibility of this new transformation. Subsequent studies will optimize the process through convenient yet systematic modifications to the peptidyl ligand structure of the novel catalytic system; developing a better mechanistic understanding of the reaction, and applying this transformation toward the synthesis of various anti-HIV agents. Similarly, the addition of trimethylsilylcyanide to imines (Strecker reaction) will be developed into a general catalytic asymmetric transformation. Again the scope of the reaction will be delineated with catalysts containing metals coordinated to peptidic ligands. Reaction mechanism will be probed and applications toward important molecules will be demonstrated. Both of the reactions to be developed will employ Lewis acidic metals that are modified with chiral peptidyl ligands as catalysts. Of particular significance is the speed at which the new catalysts can be prepared and optimized. This unique and useful feature is the direct result of using amino acids as the chiral building blocks of the ligand system. Since amino acids are readily available and peptide synthesis has been worked out in both solution and solid phase, simultaneous preparation of multiple ligand structures is relatively straightforward. The large number of ligands that can be prepared and screened for both reactivity and selectivity in a systematic manner allows for the rapid selection of an optimal catalytic system.