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.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

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

参考文献 17

[1]	Cabré, A.; Verdaguer, X.; Riera, A. Chem. Rev. 2022, 122, 269.
[2]	(a) Peluso, P.; Chankvetadze, B. Chem. Rev. 2022, 122, 13235.
	(b) Coelho, M. M.; Fernandes, C.; Remião, F.; Tiritan, M. E. Molecules 2021, 26, 3113.
[3]	Liu, H.; Wu, Z.; Chen, J.; Wang, J.; Qiu, H. J. Chromatogr. A 2023, 1708, 464367.
[4]	(a) Chai, Z.; Wang, W.; Chen, J.; Wu, Q.; Ma, L.; Liu, Z.; Xu, G.; Ling, J.; Shu, Y.; Liu, M.; Li, C. J. Am. Chem. Soc. 2026, 148, 9213.
	(b) Cui, C.-Y.; Li, B.; Zhang, X.; Guo, S.-L.; Pan, B.-B.; Su, X.-C. J. Am. Chem. Soc. 2025, 147, 19893.
	(c) Xu, Z.; Wang, C.; He, S.; Wu, J.; Zhao, Y. Angew. Chem. Int. Ed. 2025, 64, e202417112.
	(d) Chen, D.; Lin, Y.; Fan, Y.; Li, L.; Tan, C.; Wang, J.; Lin, H.; Gao, J. Angew. Chem. Int. Ed. 2023, 62, e202313753.
	(e) Zhu, W.; Monnie, C. M.; Kitoka, K.; Gronenborn, A. M. Angew. Chem. Int. Ed. 2025, 64, e202419709.
	(f) Meng, H.; Wen, L.; Xu, Z.; Li, Y.; Hao, J.; Zhao, Y. Org. Lett. 2019, 21, 5206.
[5]	(a) Wang, W.; Xia, X.; Bian, G.; Song, L. Chem. Commun. 2019, 55, 6098.
	(b) Weng, J.; Gu, G.; Zhang, W.; Jia, Q.; Sun, Y.; Wu, J.; Zhao, Y. Angew. Chem. Int. Ed. 2025, 64, e202505700.
[6]	Chen, Y.-T.; Li, B.; Chen, J.-L.; Su, X.-C. Analyst 2023, 148, 233.
[7]	Huang, B.; Xu, L.; Wang, N.; Ying, J.; Zhao, Y.; Huang, S. Anal. Chem. 2022, 94, 1867.
[8]	Jang, S.; Park, H.; Duong, Q. H.; Kwahk, E.-J.; Kim, H. Anal. Chem. 2022, 94, 1441.
[9]	(a) Gu, G.; Wang, C.; Zhao, Y. Synthesis 2025, 57, 1671.
	(b) Gu, G.; Xu, Z.; Yu, N.; Zhao, Y. Coord. Chem. Rev. 2026, 551, 217454.
[10]	(a) Zhou, Y.; Ren, Y.; Zhang, L.; You, L.; Yuan, Y.; Anslyn, E. V. Tetrahedron 2015, 71, 3515.
	(b) Ni, C.; Zha, D.; Ye, H.; Hai, Y.; Zhou, Y.; Anslyn, E. V.; You, L. Angew. Chem. Int. Ed. 2018, 57, 1300.
	(c) You, L.; Berman, J. S.; Anslyn, E. V. Nat. Chem. 2011, 3, 943.
[11]	Kriegelstein, M.; Profous, D.; Lyčka, A.; Trávníček, Z.; Přibylka, A.; Volná, T.; Benická, S.; Cankař, P. J. Org. Chem. 2019, 84, 11911.
[12]	Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512.
[13]	(a) Jolliffe, J. D.; Armstrong, R. J.; Smith, M. D. Nat. Chem. 2017, 9, 558.
	(b) Pu, L. Chem. Rev. 2024, 124, 6643.
[14]	(a) Pu, L. Acc. Chem. Res. 2012, 45, 150.
	(b) Pu, L.; Senge, M. O.; Olmstead, M. M.; Power, P. P. J. Am. Chem. Soc. 1998, 120, 12682.
	(c) Yu, H.-B.; Hu, Q.-S.; Pu, L. J. Am. Chem. Soc. 2000, 122, 6500.
	(d) Pu, L. Chem. Rev. 2004, 104, 1687.
[15]	Li, Y.; Wen, L.; Meng, H.; Lv, J.; Luo, G.; Zhao, Y. Cell Rep. Phys. Sci. 2020, 1, 100100.
[16]	Ma, Z.; Gu, G.; Zeng, Y.; Weng, J.; Bao, W.; Zhao, Y. Talanta 2026, 298, 129057.
[17]	(a) Li, H.; Xu, Z.; Zhang, S.; Jia, Y.; Zhao, Y. Anal. Chem. 2022, 94, 2023.
	(b) Dong, C.; Xu, Z.; Wen, L.; He, S.; Wu, J.; Deng, Q.-H.; Zhao, Y. Anal. Chem. 2021, 93, 2968.

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

RichHTML

PDF

补充材料

可视化

摘要/Abstract

引用此文

分享此文

图/表 7

参考文献 17

相关文章 15

编辑推荐

相关统计

本文评价

[1]	肖忠闪, 王涵, 徐露, 何瑞娟, 杨国静, 王亚坤, 刘兆敏, 张涛. 用于二氧化硫衍生物检测与成像的新型磷酸酯-吩噻嗪荧光探针[J]. 有机化学, 2026, 46(8): 3068-3078.
[2]	陈珪媛, 李晟宇, 郭基林, 王相, 刘烨潼, 肖贝宁, 汪朝阳. 3-氰基吡啶类化合物的合成与应用研究进展[J]. 有机化学, 2026, 46(6): 2227-2240.
[3]	郭百淋, 王赛女, 雷炳新, 王恩举. 基于单体-激基缔合物荧光转换的免洗细胞膜荧光探针[J]. 有机化学, 2026, 46(5): 2082-2089.
[4]	张继东, 王浩, 权校昕, 张胜海, 厍伟. 基于四苯乙烯结构的聚集诱导发光效应(AIE)有机多晶体合成: 分子构象和Cys检测性能研究[J]. 有机化学, 2026, 46(3): 934-940.
[5]	刘琳, 周璐璐, 梁天宇, 钟克利, 燕小梅, 汤立军. 基于苯并吡喃衍生物的近红外荧光探针用于二氧化硫衍生物的高灵敏检测与生物成像[J]. 有机化学, 2026, 46(3): 866-871.
[6]	孙小飞, 张海媛, 李娟, 马骥, 王若溪, 钟克利, 李学鹏, 梁天宇, 汤立军, 励建荣. 基于“OFF-ON”型荧光探针的智能一体化平台在三文鱼肉新鲜度监测中的应用[J]. 有机化学, 2026, 46(2): 586-593.
[7]	顾运琼, 姚嘉伟, 钟智薇, 文舒婷, 杨坤, 刘亚璐, 甘春芳. 氨基酸修饰的孕甾衍生物设计合成及抗肿瘤活性研究[J]. 有机化学, 2026, 46(2): 545-553.
[8]	杨洁, 佘湫楠, 周逸聪, 康丽琴, 赵佳丽, 刘传祥. 氰基导向芳香氢亲核取代反应构建新型萘酰亚胺比色探针: 食品与水样中氰化物的高灵敏检测[J]. 有机化学, 2026, 46(2): 531-538.
[9]	任钶, 张光露, 牛轶凡, 王晓萌, 陈灿玉, 蒋敏. 光催化合成含氮杂芳环非天然氨基酸[J]. 有机化学, 2026, 46(1): 215-224.
[10]	姜志洁, 陈锦秀, 朱晓菲, 邓鑫浩, 严琼姣, 汪伟, 周慧. 噁唑酮不同活性位点的官能团化反应研究进展[J]. 有机化学, 2026, 46(1): 1-20.
[11]	彭澳霈, 李扬, 朱园园, 吴广文, 古双喜. 席夫碱型荧光探针对氨基酸化学选择性识别研究进展[J]. 有机化学, 2025, 45(9): 3301-3313.
[12]	李兆周, 谢亚芳, 陶健, 魏雪冰, 黎乐乐, 李亚娟, 唐嘉敏, 牛华伟, 陈秀金, 高红丽, 李芳, 于慧春, 袁云霞, 古绍彬, 康怀彬, 孙晓菲, 任国艳, 吴影. 半胱氨酸荧光探针的构建及其在病理学检验中的应用[J]. 有机化学, 2025, 45(7): 2335-2349.
[13]	沈晴, 曾玉, 黎忠昊, 曹西颖, 郭玉婷, 叶蕴仪, 汪朝阳. 基于共价键形成与切断的反应型小分子荧光探针的研究进展[J]. 有机化学, 2025, 45(4): 1194-1205.
[14]	张文博, 苏思铭, 杨鹏. 新型杯[3]咔唑衍生物的合成及其对羟喜树碱识别与检测研究[J]. 有机化学, 2025, 45(4): 1395-1401.
[15]	相韩悦, 魏少荫, 王玉记, 肖猱. 基于N-氧化物结构Fe^2＋荧光探针的研究进展[J]. 有机化学, 2025, 45(4): 1137-1152.