6-(4-氯苯氧基)四唑并[5,1-a]酞嗪的核磁共振谱峰归属

doi:10.11938/cjmr20192776

波谱学杂志 ›› 2020, Vol. 37 ›› Issue (3): 390-398.doi: 10.11938/cjmr20192776

6-(4-氯苯氧基)四唑并[5,1-a]酞嗪的核磁共振谱峰归属

王思宏¹, 张敬东¹, 尹秀梅¹, 李东浩¹, 阚玉和², 胡伟³

1. 延边大学, 分析测试中心, 吉林延吉 133002;
2. 淮阴师范学院化学化工学院, 江苏淮安 223300;
3. 广东省石油与精细化工研究院, 广东广州 510665

收稿日期:2019-08-09 出版日期:2020-09-05 发布日期:2019-12-13
通讯作者: 阚玉和,Tel:0517-83525100-1,E-mail:kyh@hytc.edu.cn;胡伟,Tel:020-32373090,E-mail:gracehz@126.com. E-mail:kyh@hytc.edu.cn;gracehz@126.com
基金资助:
国家自然科学基金资助项目（21964017，21365023）；广东省科学院实施创新驱动发展能力建设专项（2018GDASCX-0802）

NMR Assignments of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine

WANG Si-hong¹, ZHANG Jing-dong¹, YIN Xiu-mei¹, LI Dong-hao¹, KAN Yu-he², HU Wei³

1. Analysis and Inspection Center, Yanbian University, Yanji 133002, China;
2. School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huai'an 223300, China;
3. Guangdong Research Institute of Petrochemical and Fine Chemical Engineering, Guangzhou 510665, China

Received:2019-08-09 Online:2020-09-05 Published:2019-12-13

1. 补充材料.pdf(304KB)

摘要/Abstract

摘要： 为确保具有独立知识产权的国家级一类抗癫痫创新候选药物的药品安全，采用500 MHz核磁共振（NMR）技术，结合规范不变原子轨道-核磁共振（GIAO-NMR）量子化学计算方法，对进入临床阶段的抗癫痫药6-（4-氯苯氧基）四唑并[5，1-a]酞嗪的¹H NMR、¹³C NMR和¹⁵N NMR信号进行了归属，从而为安全用药提供了精确结构信息．线性回归对比表明，标度法计算的NMR化学位移与实验值吻合较好．

关键词: 液体NMR, 结构归属, 二维NMR, ¹⁵N NMR, 6-(4-氯苯氧基)四唑并[5,1-a]酞嗪, 密度泛函理论计算

Abstract: 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine is a national class I innovative antiepileptic drug candidate in clinical trials with independent intellectual property rights. The ¹H, ¹³C and ¹⁵N NMR spectra of the compound were acquired at 500 MHz. Aided by GIAO (Gauge-Independent Atomic Orbital)-NMR quantum chemistry calculation, the chemical shifts of the compound were assigned, providing elaborate structural information of the compound. Linear regression comparison results showed good consistency between the theoretical predictions and the experimental data for structural elucidations.

Key words: liquid-state NMR, structural assignment, 2D NMR, ¹⁵N NMR, 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine, density functional theory calculation

中图分类号:

O656.4

王思宏, 张敬东, 尹秀梅, 李东浩, 阚玉和, 胡伟. 6-(4-氯苯氧基)四唑并[5,1-a]酞嗪的核磁共振谱峰归属[J]. 波谱学杂志, 2020, 37(3): 390-398.

WANG Si-hong, ZHANG Jing-dong, YIN Xiu-mei, LI Dong-hao, KAN Yu-he, HU Wei. NMR Assignments of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine[J]. Chinese Journal of Magnetic Resonance, 2020, 37(3): 390-398.

参考文献

[1] 国家药典委员会. 核磁共振波谱法[S]//中华人民共和国药典四部. 2020年版. 北京:中国医药科技出版社, 2020:0441.
[2] WANG Y L, WANG X J, WANG Z W. Spectral analyses and structural elucidation of azilsartan[J]. Chinese J Magn Reson, 2019, 36(3):350-358.王亚兰, 王晓静, 王志伟. 阿齐沙坦的波谱学数据及结构确证[J]. 波谱学杂志, 2019, 36(3):350-358.
[3] WEI H Q, YU J, BI C F, et al. An NMR study of N-isobutyryl-3'-O-(1-fluoro-1,1,3,3-tetraisopropyl-1,3-disiloxane-3-yl)-2'-benzyloxycarbonyl-guanosine[J]. Chinese J Magn Reson, 2019, 36(1):93-102.魏会强, 于江, 毕常芬, 等. N-异丁酰基-3'-O-(1-氟-1,1,3,3-四异丙基-1,3-二硅氧烷-3-基)-2'-苄氧羰基鸟苷的NMR研究[J]. 波谱学杂志, 2019, 36(1):93-102.
[4] WANG S H, KAN Y H. Experimental and theoretical studies of the absolute configuration of (2S,1'R) and (2R,1'R)-2-acetoxymethyl-3-phenyl-N-(1'-phenylethyl)-propionamide[J]. Journal of Molecular Structure, 2010, 981(1):159-162.
[5] WANG S H, YIN X M, KAN Y H, et al. Assignment of carbon and proton chemical shifts of 3-nitrobenzanthron[J]. Journal of Yanbian Uviversity (Natural Science), 2012, 38(2):138-141.王思宏, 尹秀梅, 阚玉和, 等. 3-硝基苯并蒽酮的碳和氢的化学位移归属[J]. 延边大学学报(自然科学版), 2012, 38(2):138-141.
[6] LI X, ZHANG H J, WANG Q, et al. Current study of the mechanism of action of the potential anti-epileptic agent Q808[J]. Molecules, 2017, 22(7):1134.
[7] SUN X Y, WEI C X, DENG X Q, et al. Evaluation of the anticonvulsant activity of 6-(4-chlorophenyoxy)-tetrazolo[5,1-a]phthalazine in various experimental seizure models in mice[J]. Pharmacol Rep, 2010, 62(2):273-277.
[8] YU H L, ZHANG F, LAN T, et al. Effects of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine on anticoagulation in mice and the inhibition of experimental thrombosis in rats[J]. J Cardiovasc Pharmacol, 2014, 64(6):560-566.
[9] YU H L, ZHANG F, LI Y J, et al. Anti-inflammatory and antinociceptive effects of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine in mice[J]. Pharmacol Rep, 2012, 64(5):1155-1165.
[10] ZHANG F, JIANG H C, CHEN X R, et al. Antidepressant-like effect of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine in mice[J]. Chin J Pharm Toxicol, 2013, 27(5):783-788.
[11] SUN X Y, WEI C X, DENG X Q, et al. Synthesis and primary anticonvulsant activity evaluation of 6-alkyoxyl-tetrazolo[5,1-a]phthalazine derivatives[J]. Arzneim Forsch, 2010, 60(6):289-292.
[12] LI L, LIU C, QUAN Z S, et al. Structure identification and determination of therelated substances in the first type of new anti-epileptic drug Q808[J]. Journal of Yanbian Uviversity (Natural Science), 2016, 39(2):103-107.李龙, 刘冲, 全哲山, 等. 抗癫痫一类新药Q808有关物质的结构确定及含量测定[J]. 延边大学医学学报, 2016, 39(2):103-107.
[13] WOLINSKI K, HINTON J F, PULAY P. Efficient implementation of the gauge-independent atomic orbital method for NMR chemical shift calculations[J]. J Am Chem Soc, 1990, 112(23):8251-8260.
[14] JENSEN F. Segmented contracted basis sets optimized for nuclear magnetic shielding[J]. J Chem Theory Comput, 2015, 11(1):132-138.
[15] GAUSS J. Calculation of NMR chemical shifts at second-order many-body perturbation theory using gauge-including atomic orbitals[J]. Chem Phys Lett, 1992, 191(6):614-620.
[16] LODEWYK M W, SIEBERT M R, TANTILLO D J. Computational prediction of ¹H and ¹³C chemical shifts:a useful tool for natural product, mechanistic, and synthetic organic chemistry[J]. Chem Rev, 2012, 112(3):1839-1862.
[17] GAO P, WANG X, YU H. Towards an accurate prediction of nitrogen chemical shifts by density functional theory and gauge-including atomic orbital[J]. Adv Theor Simul, 2019, 2(2):1800148.
[18] 于德泉, 杨峻山. 分析化学手册:核磁共振波谱分析[M]. 北京:化学工业出版社, 1999.
[19] 孔令义. 复杂天然产物波谱解析[M]. 北京:中国医药科技出版社, 2012.
[20] CMOCH P, STEFANIAK L, MELZER E, et al. ¹H, ¹³C and ¹⁵N NMR study of some triazolo-and tetrazolopyridazines and thioxotriazolopyridines[J]. Magn Reson Chem, 1999, 37(7):493-497.
[21] STEFANIAK L, ROBERTS J D, WITANOWSKI M, et al. A nitrogen-15 NMR investigation of some azolopyridines[J]. Org Magn Reson, 1984, 22(4):209-214.
[22] XU X, ZHU C L, KAN Y H. Sensing mechanism and molecular design of FRET based dual-emission fluorescent probe[J]. Journal of Huaiyin Teachers College (Natural Science Edition), 2019, 18(1):41-47.徐鑫, 朱长磊, 阚玉和. 基于FRET的双发射荧光探针的传感机理及分子设计[J]. 淮阴师范学院学报(自然科学版), 2019, 18(1):41-47.

6-(4-氯苯氧基)四唑并[5,1-a]酞嗪的核磁共振谱峰归属

NMR Assignments of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine

PDF

补充材料

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	柴鑫, 孙鹏, 袁斌, 肖雄杰, 张许, 刘买利. 乳制品中胆碱及其衍生物的快速核磁共振检测[J]. 波谱学杂志, 2018, 35(2): 178-187.
[2]	周琪, 黄重阳, 高珊, 汪慧娟, 冯继文, 刘朝阳, 张金枝, 邹其超. 基于自主研发的500 MHz NMR谱仪的紫杉醇结构解析[J]. 波谱学杂志, 2017, 34(1): 52-60.
[3]	孙伟, 高翔, 郭娟, 余向阳. 洛莫司汀的¹H、¹³C NMR全归属[J]. 波谱学杂志, 2016, 33(2): 353-359.
[4]	王喆, 冯玉萍, 刘林园, 单璐, 赵玉芬. 天然丰度的N-磷酰化氨基酸的¹⁵N NMR 研究[J]. 波谱学杂志, 2009, 26(4): 512-517.
[5]	王琳. 表面官能化碳纳米管¹³C NMR参数的理论研究[J]. 波谱学杂志, 2009, 26(2): 230-238.
[6]	李临生1,2 ; 张丽娜1,2 ; 兰云军1 ; 张昌辉2 . 取代亚胺中亚胺基¹⁵N NMR化学位移规律的研究[J]. 波谱学杂志, 2008, 25(3): 391-396.
[7]	张丽娜, 李临生, 兰云军, 李利东. 脂肪胺类化合物氨基¹⁵N NMR 化学位移规律的研究[J]. 波谱学杂志, 2006, 23(2): 225-240.
[8]	孙平川, 陈铁红, 伍国琳, 李宝会, 金庆华, 丁大同. 高聚物微观结构的固体NMR研究[J]. 波谱学杂志, 2004, 21(1): 141-147.
[9]	王淘淘, 汪汉卿, 韩秀文, 朱明, 魏孝义, 韦壁瑜. 宿萼假耧斗菜有效组分的NMR研究[J]. 波谱学杂志, 1995, 12(6): 641-648.
[10]	裴奉奎, 刘爱琢, 张善荣. 多维核磁共振波谱学[J]. 波谱学杂志, 1995, 12(4): 379-390.
[11]	杨宪斌, 邹坤, 姚冰, 张如意. 胀果香豆素甲的NMR研究[J]. 波谱学杂志, 1994, 11(4): 399-403.
[12]	江忝益, 洪美芳, 潘竞先, 杨宪斌. 崖椒根中两个新化合物的NMR研究[J]. 波谱学杂志, 1992, 9(4): 413-417.
[13]	刘吉开, 韩秀文, 吴大刚, 贾忠健. 南蛇藤中倍半萜生物碱的二维NMR研究[J]. 波谱学杂志, 1992, 9(3): 289-295.
[14]	吴家振, 周淑华. 高铁细胞色素C碱性异构体的NMR研究[J]. 波谱学杂志, 1992, 9(1): 51-57.
[15]	桑鸿, 汪汉卿, 涂永强. NOE和二维NMR技术在倍半萜化学位移归属中的应用[J]. 波谱学杂志, 1991, 8(1): 19-28.