非均匀采样在小分子化合物结构鉴定中的应用策略——以附子灵为例  

The application strategies of non-uniform sampling in the structure elucidation of small molecule compounds-an instantiation using fuziline

作　　者：张莉莉 张可 刘杰 蒙春旺 冯芮 熊亮[1,2] ZHANG Li-li;ZHANG Ke;LIU Jie;MENG Chun-wang;FENG Rui;XIONG Liang(State Key Laboratory of Southwestern Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;School of Medical Technology,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)

机构地区：[1]成都中医药大学药学院,西南特色中药资源国家重点实验室,四川成都611137 [2]成都中医药大学医学技术学院,四川成都611137

出　　处：《药学学报》2025年第1期218-224,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金青年基金(82104546);四川省科技创新创业苗子工程(2023JDRC0122);四川省自然科学基金(2024NSFSC1830)。

摘　　要：二维核磁共振(2D NMR)是一种广泛应用于小分子化合物结构解析的技术,可获得化合物的氢-氢相关、氢-碳单键相关、氢-碳远程相关及氢-氢空间排布等信息,在小分子化合物结构鉴定中具有不可替代的作用。然而植物化学研究中微量成分的样品量极低,采用传统采样方法(即均匀采样法)存在谱图质量较差和耗时过长的问题。通过增大扫描次数会导致单个二维谱的采集时间长达数小时,这又引起核磁共振仪机时紧张的问题。非均匀采样(non-uniform sampling,NUS)技术在保证2D NMR谱图质量的同时,还可较大程度缩短数据采集时间,这大大提高了二维谱图采集的效率。本文选择附子药材中小分子化合物——附子灵为研究对象,以均匀采样(uniform sampling,US)和NUS方法分别采集其1H-^(13)C HSQC、^(1)H-^(1)H COSY、HMBC和NOESY谱,对比两种采样方法的附子灵中三类基团核磁信号的积分值,证实了NUS技术在小分子化合物结构鉴定中具有提高谱图质量和缩短采集时间的优势;并在HMBC谱中,进一步证实了NUS技术能提高二维谱图质量和信号分辨率,表明NUS技术可提高小分子化合物结构鉴定的效率和可靠性。Two-dimensional nuclear magnetic resonance(2D NMR)is a widely used technique for structural analysis of small molecular compounds.It can obtain information about the hydrogen-hydrogen correlation,hydrogen-carbon single bond correlation,hydrogen-carbon remote correlation,and hydrogen-hydrogen spatial arrangement of compounds.Thus,2D NMR has an irreplaceable role in the structure elucidation of small molecular products.However,the sample amount of trace components in phytochemical research is very low,and the traditional sampling method(uniform sampling)has problems of poor spectral quality and too long measure time.Increasing the number of scans results in several hours of the acquisition time for a single two-dimensional spectrum,which in turn causes strain on the NMR machine.The non-uniform sampling(NUS)technique can shorten the acquisition time to a large extent and not affect the quality of 2D NMR data,which greatly improves the efficiency of 2D NMR acquisition.In this paper,fuziline,a small molecular compound in the lateral roots of Aconitum carmichaeli was selected as the research object.Its1H-^(13)C HSQC、^(1)H-^(1)H COSY、HMBC,and NOESY spectra were acquired by US and NUS methods,respectively.By comparing the integral values of NMR signals of three chemical groups in fuziline,it is confirmed that the NUS technique has the advantages of improving the quality of 2D NMR spectra and shortening the acquisition time in structure elucidation of small molecule compounds.In HMBC spectrum,it was further confirmed that NUS technology can improve the quality of the 2D spectra and the signal resolution.This indicates that NUS technology can improve the efficiency and reliability of the structure elucidation of small molecule compounds.

关 键 词：核磁共振 二维核磁共振谱图 非均匀采样 小分子化合物 附子灵 

分 类 号：R917[医药卫生—药物分析学]