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不对称催化的通用性筛选
作者:小柯机器人 发布时间:2022/9/3 20:48:02

美国哈佛大学Jacobsen, Eric N.研究团队报道了不对称催化的通用性筛选。相关研究成果发表在2022年9月1日出版的国际知名学术期刊《自然》。

在过去半个世纪中,不对称催化领域的研究取得了里程碑式的进展,使手性构建块、药物和天然产物的高效合成成为可能。已鉴定出少量不对称催化反应,其在广泛的底物范围内显示出高选择性;并非巧合的是,这些反应对合成对映体富集化合物的影响最大。研究人员认为不对称催化中的底物普遍性很罕见,不仅因为其本质上难以实现,而且还因为手性催化剂的识别和优化方式。典型的发现依赖于单一模型基质,因此选择在狭窄的化学空间区域内实现高性能。

该文中,研究人员从一开始就提出了一种在不对称催化反应中,使用多个模型底物同时选择对映选择性和通用性的实用方法。采用超临界流体色谱-质谱(SFC-MS)对混合样品进行高通量手性分析,实现多底物筛选。当应用于Pictet–Spengler反应时,多底物筛选方法揭示了这一重要转化的一般对映选择性催化的一个有希望和出乎意料的结果,甚至对筛选集之外的底物组合显示了高对映选择性。

附:英文原文

Title: Screening for Generality in Asymmetric Catalysis

Author: Wagen, Corin C., McMinn, Spencer E., Kwan, Eugene E., Jacobsen, Eric N.

Issue&Volume: 2022-09-01

Abstract: Research in the field of asymmetric catalysis over the past half century has resulted in landmark advances, enabling the efficient synthesis of chiral building blocks, pharmaceuticals, and natural products.1-3 A small number of asymmetric catalytic reactions have been identified that display high selectivity across a broad scope of substrates; not coincidentally, these are the reactions that have the greatest impact on how enantioenriched compounds are synthesized.4–8 We postulate that substrate generality in asymmetric catalysis is rare not simply because it is intrinsically difficult to achieve, but also because of the way chiral catalysts are identified and optimized.9 Typical discovery campaigns rely on a single model substrate, and thus select for high performance in a narrow region of chemical space. Here, we put forth a practical approach for using multiple model substrates to select simultaneously for both enantioselectivity and generality in asymmetric catalytic reactions from the outset.10,11 Multi-substrate screening is achieved by conducting high-throughput chiral analyses via supercritical fluid chromatography-mass spectrometry (SFC-MS) with pooled samples. When applied to Pictet–Spengler reactions, the multi-substrate screening approach revealed a promising and unexpected lead for the general enantioselective catalysis of this important transformation which even displayed high enantioselectivity for substrate combinations outside of the screening set.

DOI: 10.1038/s41586-022-05263-2

Source: https://www.nature.com/articles/s41586-022-05263-2

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:42.778
官方网址:http://www.nature.com/