Chirality imprinting and direct asymmetric reaction screening using a stereodynamic Brønsted/Lewis acid receptor.
Chirality imprinting and direct asymmetric reaction screening using a stereodynamic Brønsted/Lewis acid receptor.
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DOI：
10.1038/ncomms12539
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发表时间：
2016-08-23
影响因子：
16.6
通讯作者：
Wolf C
中科院分区：
文献类型：
--
作者：
Bentley KW;Proano D;Wolf C
分子识别、活化和与布朗斯特酸和刘易斯酸的动态自组装在化学科学中起着核心作用，包括催化、晶体工程、超分子结构和药物设计。尽管这一普遍的进步，利用相应的结合基序的快速和强大的定量化学传感的手性化合物在一个复杂的矩阵仍然具有挑战性。在这里，我们表明，立体动力学探针携带互补硼酸和尿素单元实现这一目标与羟基羧酸。协同双位点结合和瞬时手性印迹导致特征紫外和CD读数，允许即时测定目标化合物的绝对构型、对映体过量和浓度，即使在复杂的混合物中。这种策略的鲁棒性和实用性的高通量筛选的目的是证明。仅对0.5 mg不对称还原的粗反应混合物进行全面检测，消除了繁琐的后处理方案，并最大限度地减少了分析时间、劳动力和废物产生。 测定不对称反应的结果可能需要很长的时间，并且在后处理和分析期间消耗大量的有机溶剂。在这里，作者报道了一种双功能有机探针，可以结合到手性羟基酸，并提供产率，对映体过量和绝对构型，甚至与粗混合物。
Molecular recognition, activation and dynamic self-assembly with Brønsted and Lewis acids play a central role across the chemical sciences including catalysis, crystal engineering, supramolecular architectures and drug design. Despite this general advance, the utilization of the corresponding binding motifs for fast and robust quantitative chemosensing of chiral compounds in a complicate matrix has remained challenging. Here we show that a stereodynamic probe carrying complementary boronic acid and urea units achieves this goal with hydroxy carboxylic acids. Synergistic dual-site binding and instantaneous chirality imprinting result in characteristic ultraviolet and CD readouts that allow instantaneous determination of the absolute configuration, enantiomeric excess and concentration of the target compound even in complex mixtures. The robustness and practicality of this strategy for high-throughput screening purposes is demonstrated. Comprehensive sensing of only 0.5 mg of a crude reaction mixture of an asymmetric reduction eliminates cumbersome work-up protocols and minimizes analysis time, labour and waste production. Determining results of asymmetric reactions can take long periods of time and consume large amounts of organic solvents during work-up and analysis. Here, the authors report a bifunctional organic probe that can bind to chiral hydroxyacids, and provide yield, enantiomeric excess and absolute configuration even with crude mixtures.