Refining & Implementing Supramolecular Methods for HTS of EE & Concentration

描述（由申请人提供）：最近，由于用于不对称反应发现和优化的高通量筛选（HTS）协议的出现，对ee的用户友好和快速检测的需求日益增加。许多研究需要数百次分析，但真正的高通量筛选必须每天容纳数千次分析。这对于目前被广泛接受的ee分析方法来说是不可能的。本次更新申请的主要目标是实现我们之前开发的催化不对称反应筛选中对映异构体过量（ee）和反应产率的高通量筛选分析。在这个项目中，我们将率先将光学高温超导方法过渡到合成方法化学家的工作实验室。我们的方法结合了超分子化学和化学计量学的ee的高温超导。我们创造了非常简单的合成受体，针对手性官能团的类别，并记录了非对映体或对映体络合物形成的吸光度或圆二色光谱。LDA、PCA或ANN解释光学数据。分析在微滴板中进行，其中ee值以及浓度（反应产率），96个粗反应混合物可以在1分钟至2小时内读取，具体取决于具体的分析。在下一个资助期内，我们的第一个目标将是完成一些几乎可操作的手性官能团（伯胺、羧酸和酮）的测定，我们将设计一个手性仲醇的测定。其次，为了在现实生活中实施我们的分析，我们与合成方法化学家建立了三个合作关系：张（罗格斯大学），米勒（耶鲁大学）和克里什（奥斯汀大学）。这三个项目将采用我们的HTS方法对伯胺、羧酸和仲醇进行不对称催化反应的发现和优化。因此，这个建议是高度可翻译的。我们的合作将测试我们的方法的实用性和普遍性，同时也突出了超分子化学和化学计量学的力量，以协助合成有机化学的努力。

DESCRIPTION (provided by applicant): The need for increasingly user-friendly and rapid assays for ee has arisen recently due the advent of high-throughput screening (HTS) protocols for asymmetric reaction discovery and optimization. Many studies require hundreds of analyses, but true high-throughput screening must accommodate thousands of assays per day. This is not possible with the methods that are currently widely accepted for ee analysis. A primary goal of this renewal application is to implement our previously developed high-throughput screening assays for enantiomeric excess (ee) and reaction yield in catalytic asymmetric reaction screening. In this project we will pioneer a transition of optical HTS methods to the working laboratories of synthetic methodology chemists. Our approach to the HTS of ee combines supramolecular chemistry with chemometrics. We create very simple synthetic receptors that are targeted to classes of chiral functional groups, and record absorbance or circular dichroism spectra for diastereomeric or enantiomeric complex formation. LDA, PCA, or ANN interprets the optical data. The analysis is performed in microtiter plates where the ee values, as well as concentration (reaction yield), of 96 crude reaction mixtures can be read within 1 minute to 2 hrs depending upon the particular assay. During the next funding period our first goal will be to complete a few assays for chiral functional groups that are almost operational (primary amines, carboxylic acids, and ketones), and we will devise an assay for chiral secondary alcohols. Second, to implement our assays in real life settings we have established three collaborations with synthetic methodology chemists: Drs. Zhang (Rutgers), Miller (Yale), and Krische (UT Austin). These three projects will implement our HTS assays for primary amines, carboxylic acids, and secondary alcohols, in asymmetric catalytic reaction discovery and optimization. Hence, this proposal is highly translational. Our collaborative efforts will test the utility and generality of our methods, while also highlighting the power of supramolecular chemistry and chemometrics to assist synthetic organic chemistry efforts. PUBLIC HEALTH RELEVANCE: is in part reliant upon pharmaceuticals. The synthetic procedures that create pharmaceuticals involve steps, which form right- and left-handed chemical structures, called enantiomers. The work described in this NIH application improves public health by creating new and faster methods for analyzing the ratios of enantiomers created during pharmaceutical development.