基于轴手性水杨醛的19F NMR探针用于手性胺的对映体识别

doi:10.6023/cjoc202603044

摘要/Abstract

发展简便、普适的¹⁹F NMR手性分析方法用于一级胺识别仍存在挑战, 因为有效的探针设计需要在同一分子中同时整合刚性的手性环境、含氟信号报告单元以及用于快速捕获分析物的反应位点. 此文设计并合成了一种轴手性水杨醛探针S-BINOL-probe, 这是一种由[1,1'-联萘]-2,2′-二醇(BINOL)衍生而来的轴手性水杨醛探针, 并引入了三氟乙氧基作为信号报告基团. 该探针可由商业可得的起始原料经简短步骤制备而成, 并能够与分析物形成非对映亚胺加合物, 从而产生化学位移区分显著的¹⁹F NMR信号. S-BINOL-probe可用于区分15种手性一级胺、广泛的氨基酸底物、多组分氨基酸混合物以及具有代表性的手性胺类药物. 同一平台还可实现对映体组成的准确测定, 测得的对映体过量值(ee)与配制的ee之间表现出优异的线性关系. 这些结果表明, S-BINOL-probe是一种合成简便易得, 且在分析上具有实用价值的¹⁹F NMR检测试剂, 可用于快速手性分析.

关键词: 核磁共振氟谱, 探针, 手性分析, 氨基酸, 对映体过量值

A concise and broadly applicable strategy for the chiral analysis of primary amines by ¹⁹F NMR remains difficult to realize because an effective probe must integrate a rigid chiral environment, a fluorinated reporter, and a reactive site for fast analyte capture. S-BINOL-probe, an axially chiral salicylaldehyde derived from 1,1'-bi-2-naphthol (BINOL) and equipped with a trifluoroethoxy reporter, is reported in this work. The probe is prepared in a short sequence from commercially available starting materials and forms diastereomeric imine adducts that display well-resolved ¹⁹F NMR signals. S-BINOL-probe discriminates 15 chiral primary amines, a broad set of amino acids, multicomponent amino acid mixtures, and representative chiral amine drugs. The same platform also enables accurate determination of enantiomeric composition, and the measured ee exhibits excellent linear correlation with preset ee. These results identify S-BINOL-probe as a synthetically accessible and analytically useful ¹⁹F NMR sensing reagent for rapid chiral analysis.

Key words: ¹⁹F NMR, probe, chiral analysis, amino acids, enantiomeric excess

引用此文

彭天赐, 翁嘉劲, 谷广星, 赵延川. 基于轴手性水杨醛的¹⁹F NMR探针用于手性胺的对映体识别[J]. 有机化学, 2026, 46(9): 3704-3712.

Tianci Peng, Jiajin Weng, Guangxing Gu, Yanchuan Zhao. An Axially Chiral Salicylaldehyde-Based ¹⁹F NMR Probe for the Enantiomeric Discrimination of Chiral Amines[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3704-3712.

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图/表 7

Scheme 1. (a ~ c) Comparison of established 19F NMR derivatization strategies; (d) Axially chiral BINOL-derived dynamic covalent probe developed in this work

Scheme 2. Preparation of the 19F-Labeled derivatization reagent S-BINOL-probe

Figure 1. Chiral recognition of amine compounds by 19F NMR using the probe S-BINOL-probe The 19F NMR spectra of mixtures of S-BINOL-probe (2.54 mmol/L) with different racemic analytes (2.54 mmol/L) in CD3OD. The 19F NMR spectra were recorded on a Bruker AVANCE NEO 600 NMR spectrometer (565 MHz for 19F) with 32 scans.

Figure 2. Chiral discrimination of amines by 19F NMR using the probe S-BINOL-probe (a~k) 19F NMR spectra of mixtures containing S-BINOL-probe (2.54 mmol/L, pre-dissolved in 400 µL of CD3OD) and various racemic analytes (5.08 mmol/L, dissolved in 100 µL of H2O with 75.2 mmol/L NEt3), resulting in a final CD3OD/H2O (V∶V=4∶1); (l~p) 19F NMR spectra of mixtures containing S-BINOL-probe (2.54 mmol/L, pre-dissolved in 400 µL of DMSO-d6) and various racemic analytes (5.08 mmol/L, dissolved in 100 µL of H2O with 75.2 mmol/L NEt3), resulting in a final DMSO-d6/H2O (V∶V=4∶1). 19F NMR spectra were recorded on a Bruker AVANCE NEO 600 NMR spectrometer (565 MHz for 19F) with 32 scans.

Figure 3. 19F NMR spectra (32 scans) of mixtures of the probe S-BINOL-probe (2.54 mmol/L in CD3OD) and different analytes (5.08 mmol/L in H2O with 75.2 mmol/L NEt3) (a) Spectra obtained after pre-mixing the four amino acid analytes and then adding the mixture to probe S-BINOL-probe; (b~e) spectra of probe S-BINOL-probe bound to various amino acid compounds; (f) probe S-BINOL-probe alone.

Figure 4. Linear regression plot showing the relationship between the prepared ee and the ee of B8S measured using the probe S-BINOL-probe

Figure 5. (a~b) 19F NMR spectra of the probe S-BINOL-probe (2.54 mmol/L) mixed with various chiral amine drugs (5.08 mmol/L in H2O with 75.2 mmol/L NEt3) in DMSO-d6; (c~f) 19F NMR spectra of the probe S-BINOL-probe (2.54 mmol/L) mixed with various chiral amine drugs (5.08 mmol/L) in DMSO-d6

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基于轴手性水杨醛的¹⁹F NMR探针用于手性胺的对映体识别

An Axially Chiral Salicylaldehyde-Based ¹⁹F NMR Probe for the Enantiomeric Discrimination of Chiral Amines

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