硫辛酸酯类衍生物的合成及生物活性

doi:10.7503/cjcu20180270

高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (10): 2198.doi: 10.7503/cjcu20180270

硫辛酸酯类衍生物的合成及生物活性

张露云^1,², 徐倩^2,³, 夏广清^1,², 丛丽², 王雨², 张辉¹, 朱俊义²(), 臧皓^2,³()

1. 长春中医药大学吉林省人参科学研究院, 长春 130117
2. 通化师范学院医药学院, 绿色药物化学实验室, 通化 134002
3. 延边大学药学院, 延吉 133000

收稿日期:2018-04-09 出版日期:2018-10-10 发布日期:2018-09-10
作者简介:联系人简介: 臧皓, 男, 博士, 副教授, 主要从事药物化学方面的研究. E-mail: zanghao_1984@163.com;朱俊义, 男, 博士, 教授, 主要从事生物活性方面的研究. E-mail: swx0527@163.com
基金资助:
吉林省科技发展计划项目(批准号: 20160520044JH)和吉林省中医药管理局科技项目(批准号: 2017110)资助.

Synthesis and Biological Activity of Lipoic Acid Ester Derivatives^†

ZHANG Luyun^1,², XU Qian^2,³, XIA Guangqing^1,², CONG Li², WANG Yu², ZHANG Hui¹, ZHU Junyi^2,^*(), ZANG Hao^2,^3,^*()

1. Jilin Ginseng Academy, Changchun University of Traditional Chinese Medicine, Changchun 130117, China
2. School of Medicine, Green Medicinal Chemistry Laboratory, Tonghua Normal University, Tonghua 134002, China
3. College of Medicine, Yanbian University, Yanji 133000, China

Received:2018-04-09 Online:2018-10-10 Published:2018-09-10
Contact: ZHU Junyi,ZANG Hao E-mail:swx0527@163.com;E-mail: zanghao_1984@163.com
Supported by:
† Supported by the Fund of Science and Technology Development of Jilin Province, China(No.20160520044JH) and the Science and Technology Projects of Administration of Traditional Chinese Medicine of Jilin Province, China(No.2017110).

摘要/Abstract

摘要：

以硫辛酸为原料, 对其羧基进行结构修饰, 合成了23个硫辛酸衍生物. 目标化合物的结构经核磁共振波谱和高分辨质谱分析确证. 生物活性测试结果表明, 在实验浓度下, 大部分化合物表现出一定的清除丙烯醛活性, 化合物3a, 3b, 3e, 3f, 3k, 3m, 3q, 3v和3w具有良好的清除丙烯醛活性, 其中化合物3a的清除活性高于对照品肌肽; 大部分化合物表现出一定的清除1,1-二苯基-2-三硝基苯肼(DPPH)活性, 化合物3o, 3p, 3v和3w具有良好的清除活性, 其中化合物3w的清除活性接近于对照品喹诺二甲基丙烯酸酯(Trolox)和维生素C; 大部分化合物表现出一定的2,2'-联氮双(3-乙基苯并噻唑啉-6-磺酸)二铵盐(ABTS)清除活性, 化合物3b, 3e, 3u, 3v和3w具有良好的清除活性, 其中化合物3w的清除活性非常接近于对照品Trolox和维生素C; 大部分化合物对铁离子-2,4,6-三(2-吡啶基)三嗪(Fe³⁺-TPTZ)复合物表现出一定的还原能力, 化合物3b, 3v和3w具有良好的还原能力, 其中化合物3w的还原能力高于对照品维生素C和Trolox; 大部分化合物表现出一定的清除羟基自由基活性, 化合物3j和3w具有良好的清除活性, 其中化合物3w的清除活性高于对照品Trolox. 血浆稳定性实验结果表明, 与硫辛酸相比, 23种化合物均具有很好的血浆稳定性.

关键词: 硫辛酸衍生物, 丙烯醛清除, 抗氧化活性, 血浆稳定性

Abstract:

A series of lipoic acid derivatives was synthesized via the modification of carboxyl groups of lipoic acid, 23 target compounds were obtained and characterized by nuclear magnetic resonance and high resolution mass spectrometry. Lipoic acid derivatives were employed in order to explore the potential structure-antioxidant activity relationships. The antioxidant activities of these compounds were evaluated and compared by the acrolein assay, 1,1-diphenyl-2-picrylhydrazyl(DPPH) assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium(ABTS) assay and ferric reducing antioxidant power(FRAP) assay. Acrolein scavenging activity test results showed that most compounds exhibited acrolein scavenging activities, compounds 3a, 3b, 3e, 3f, 3k, 3m, 3q, 3v and 3w had good acrolein scavenging activities, especially compound 3a showed the highest acrolein scavenging activity which was stronger than carnosine. The experimental results showed that most compounds exhibited DPPH scavenging activities, compounds 3o, 3p, 3v and 3w had good DPPH scavenging activities, especially compound 3w showed the highest DPPH scavenging activity, which was close to 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid(Trolox) and Vitamin C. The results showed that most compounds exhibited ABTS scavenging activities, compounds 3b, 3e, 3u, 3v and 3w had good ABTS scavenging activities, especially compound 3w showed the highest ABTS scavenging activity, which was very close to trolox and Vitamin C. FRAP experimental results showed that most compounds exhibited reduction activities to ferric ion-2,4,6-tri(2-pyridyl)-s-triazine(Fe³⁺-TPTZ) complex, compounds 3b, 3v and 3w had good reduction activities to Fe³⁺-TPTZ complex, especially compound 3w showed the highest reduction activity to Fe³⁺-TPTZ complex, which was stronger than Vitamin C and trolox. The results showed that most compounds exhibited hydroxyl radical scavenging activities, compounds 3j and 3w had good hydroxyl radical scavenging activities, especially compound 3w showed the highest hydroxyl radical scavenging activity which was stronger than trolox. Plasma stability assay results showed that compared with lipoic acid, twenty-three compounds had good plasma stability.

Key words: Lipoic acid derivative, Acrolein scavenging, Antioxidant activity, Plasma stability

中图分类号:

O623

TrendMD:

张露云, 徐倩, 夏广清, 丛丽, 王雨, 张辉, 朱俊义, 臧皓. 硫辛酸酯类衍生物的合成及生物活性. 高等学校化学学报, 2018, 39(10): 2198.

ZHANG Luyun, XU Qian, XIA Guangqing, CONG Li, WANG Yu, ZHANG Hui, ZHU Junyi, ZANG Hao. Synthesis and Biological Activity of Lipoic Acid Ester Derivatives^†. Chem. J. Chinese Universities, 2018, 39(10): 2198.

图/表 9

参考文献 33

[1]	Reed L.J., Debusk B. G., Gunsalus I. C., Hornberger C. S. Jr., Science, 1951, 114(2952), 93—94
[2]	Akiba S., Matsugo S., Packer L., Konishi T., Anal. Biochem., 1998, 258(2), 299—304
[3]	Packer L., Kraemer K., Rimbach G., Nutrition, 2001, 17(10), 888—895
[4]	Wollin S.D., Jones P. J., J. Nutr., 2003, 133(11), 3327—3330
[5]	Harrison E.H., McCormick D. B., Arch. Biochem. Biophys., 1974, 160(2), 514—522
[6]	Packer L., Tritschler H.J., Wessel K., Free. Radic. Biol. Med., 1997, 22(1/2), 359—378
[7]	Farr S.A., Poon H. F., Dogrukol-Ak D., Drake J., Banks W. A., Eyerman E., Butterfield D. A., Morley J. E., J. Neurochem., 2003, 84(5), 1173—1183
[8]	Schmidt A.M., Hori O., Brett L., Yan S. D., Wautier J. L., Stern D., Arterioscler. Thromb., 1994, 14(10), 1521—1528
[9]	Trujillo M., Radi R., Arch. Biochem. Biophys., 2002, 397(1), 91—98
[10]	Devasagayam T.P., Subramanian M., Pradhan D. S., Sies H., Chem. Biol. Interact., 1993, 86(1), 79—92
[11]	Scott B.C., Aruoma O. I., Evans P. J., O'Neil C., van der Vliet A., Cross C. E., Tritschler H., Halliwell B., Free. Radic. Res., 1994, 20(2), 119—133
[12]	Liu H.L., Niu B., Chang B. M., Cheng N. L., Xu Y. W., Zhao J. B., Chinese Remedies & Clinics, 2005, 5(1), 37—38
	(刘红林, 牛勃, 常冰梅, 程牛亮, 许言午, 赵建滨. 中国药物与临床, 2005, 5(1), 37—38)
[13]	Humphries K.M., Szweda L. I., Biochem., 1998, 37(45), 15835—15841
[14]	Pocernich C.B., Butterfield D. A., Neurotox. Res., 2003, 5(7), 515—520
[15]	Ou P., Tritschler H.J., Wolff S. P., Biochem. Pharmacol., 1995, 50(1), 123—126
[16]	Han T., Bai J., Liu W., Hu Y., Eur. J. Endocrinol., 2012, 167(4), 465—471
[17]	Papanas N., Ziegler D., Expert. Opin. Pharmacother., 2014, 15(18), 2721—2731
[18]	Hager K., Kenklies M., McAfoose J., Engel J., Munch G., J. Neural. Transm. Suppl., 2007, 72, 189—193
[19]	Erdogan M.E., Aydin S., Yanar K., Mengi M., Kansu A. D., Cebe T., Belce A., Celikten M., Cakatay U., Metab. Brain. Dis., 2017, 32(4), 1017—1031
[20]	Choi J.H., Cho S. O., Kim H., Yonsei. Med. J., 2016, 57(1), 260—264
[21]	Chang P., Liu J., Yu Y., Cui S.Y., Guo Z. H., Chen G. M., Huang Q., Liu Z. G., Cell. Physiol. Biochem., 2017, 42(6), 2559—2568
[22]	Mohammadi V., Dehghani S., Askari G., Int. J. Prev. Med., 2017, 8(1), e33
[23]	Teichert J., Kern J., Tritschler H.J., Ulrich H., Preiss R., Int. J. Clin. Pharmacol. Ther., 1998, 36(12), 625—628
[24]	Breithaupt-Grogler K., Niebch G., Schneider E., Erb K., Hermann R., Blume H.H., Schug B. S., Belz G. G., Eur. J. Pharm. Sci., 1999, 8(1), 57—65
[25]	Teichert J., Hermann R., Ruus P., Preiss R., J. Clin. Pharmacol., 2003, 43(11), 1257—1267
[26]	Bernhard N., Wolfgang S., Angew. Chem. Int. Edit., 1978, 17(7), 522—524
[27]	Appendino G., Minassi A., Daddario N., Bianchi F., Tron G.C., Org. Lett., 2002, 4(22), 3839—3841
[28]	Zang H., Sun J.M., Huang X. G., Ji Y., Dai T. T., Gao X. C., Li X. D., Zhang H., Chem. J. Chinese Universities, 2014, 35(12), 2567—2573
	(臧皓, 孙佳明, 黄晓光, 纪扬, 代婷婷, 高晓晨, 李晓东, 张辉. 高等学校化学学报, 2014, 35(12), 2567—2573)
[29]	Sharma O.P., Bhat T. K., Food Chem., 2009, 113(4), 1202—1205
[30]	Dong L.M., Jia X. C., Luo Q. W., Zhang Q., Luo B., Liu W. B., Zhang X., Xu Q. L., Tan J. W., Molecules, 2017, 22(7), e1140
[31]	Gao Y., Wang B.W., Gao S., Zhang R. H., Yang C. Y., Sun Z., Liu Z. H., Chem. Res.Chinese Universities, 2016, 32(4), 594—599
[32]	Chen C., Wang P., Zou L.W., Yang L., Fan Y. M., Hu W. Z., Ge G. B., Chem. Res.Chinese Universities, 2017, 33(2), 194—199
[33]	Guo Z., Lin D., Guo J., Zhang Y., Molecules, 2017, 22(3), e482

Compd.	Appearance	Yield(%)	m. p./℃	HRMS^, m/z*
3a	Light yellow oil	53	None	259.0329
3b	Light yellow oil	50	None	273.0487
3c	Light yellow oil	89	None	249.0877
3d	Light yellow oil	89	None	285.1959
3e	Light yellow oil	61	None	299.1490
3f	Light yellow oil	79	None	313.2271
3g	Light yellow oil	80	None	327.2429
3h	Light yellow oil	91	None	341.2583
3i	Light yellow oil	69	None	355.2741
3j	Light yellow oil	56	None	369.2899
3k	Light yellow oil	66	None	383.3055
3l	Light yellow oil	54	None	397.3211
3m	Light yellow oil	67	None	305.1645
3n	Light yellow oil	58	None	319.1805
3o	Light yellow oil	80	None	309.1594
3p	Light yellow oil	81	None	325.1368
3q	Light yellow oil	94	None	320.1755
Compd.	Appearance	Yield(%)	m. p./℃	HRMS^, m/z*
3r	Light yellow oil	77	None	323.1389
3s	Light yellow solid	84	89—90	373.1545
3t	White solid	52	101—103	362.1860
3u	Light yellow oil	58	None	353.2586
3v	Light yellow oil	80	None	349.1431
3w	Light yellow oil	47	None	365.0705

Compd.	Appearance	Yield(%)	m. p./℃	HRMS^, m/z*
3a	Light yellow oil	53	None	259.0329
3b	Light yellow oil	50	None	273.0487
3c	Light yellow oil	89	None	249.0877
3d	Light yellow oil	89	None	285.1959
3e	Light yellow oil	61	None	299.1490
3f	Light yellow oil	79	None	313.2271
3g	Light yellow oil	80	None	327.2429
3h	Light yellow oil	91	None	341.2583
3i	Light yellow oil	69	None	355.2741
3j	Light yellow oil	56	None	369.2899
3k	Light yellow oil	66	None	383.3055
3l	Light yellow oil	54	None	397.3211
3m	Light yellow oil	67	None	305.1645
3n	Light yellow oil	58	None	319.1805
3o	Light yellow oil	80	None	309.1594
3p	Light yellow oil	81	None	325.1368
3q	Light yellow oil	94	None	320.1755
Compd.	Appearance	Yield(%)	m. p./℃	HRMS^, m/z*
3r	Light yellow oil	77	None	323.1389
3s	Light yellow solid	84	89—90	373.1545
3t	White solid	52	101—103	362.1860
3u	Light yellow oil	58	None	353.2586
3v	Light yellow oil	80	None	349.1431
3w	Light yellow oil	47	None	365.0705

Compd.	¹H NMR(600 MHz), δ	¹³C NMR(150 MHz), δ
3a	3.61(q, 2H), 3.57(s, 3H), 3.18(t, 1H), 3.12(q, 1H), 2.41(d, 1H), 2.31(s, 2H), 1.87(q, 1H), 1.66(s, 1H), 1.54(d, 2H), 1.37(d, 2H)	172.8, 56.0, 51.1, 39.9, 38.1, 34.0, 33.1, 28.1, 24.2
3b	4.05(d, 2H), 3.61(q, 1H), 3.18(s, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.28(s, 2H), 1.86(q, 1H), 1.66(s, 1H), 1.54(d, 2H), 1.37(d, 2H), 1.23(s, 1H), 1.17(s, 3H)	172.8, 59.6, 56.0, 39.9, 38.1, 34.0, 33.3, 28.0, 24.2, 14.1
3c	3.96(s, 2H), 3.61(q, 1H), 3.18(q, 1H), 3.12(q, 1H), 2.41(d, 1H), 2.30(s, 2H), 1.86(q, 1H), 1.67(d, 1H), 1.57(s, 5H), 1.38(d, 2H), 0.88(s, 3H)	172.8, 65.1, 56.0, 39.9, 38.1, 34.0, 33.3, 28.1, 24.2, 21.5, 10.2
3d	4.01(s, 2H), 3.60(q, 1H), 3.18(d, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.66(s, 1H), 1.54(s, 5H), 1.33(t, 4H), 0.88(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 30.2, 28.1, 24.2, 18.6, 13.5
3e	4.00(s, 2H), 3.60(q, 1H), 3.18(d, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.66(s, 1H), 1.55(d, 5H), 1.37(s, 2H), 1.29(d, 4H), 0.87(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 28.1, 27.8, 27.6, 24.2, 21.7, 13.8
3f	4.00(s, 2H), 3.60(q, 1H), 3.18(t, 1H), 3.11(t, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(q, 1H), 1.66(s, 1H), 1.55(s, 5H), 1.37(d, 2H), 1.27(s, 6H), 0.86(s, 3H)	172.8, 63.7, 56.0, 39.9, 38.1, 34.0, 33.3, 30.8, 28.1, 28.1, 25.0, 24.2, 22.0, 13.8
3g	4.00(s, 2H), 3.60(t, 1H), 3.17(s, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(q, 1H), 1.66(t, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.26(d, 8H), 0.86(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 31.1, 28.3, 28.1, 28.0, 25.3, 24.2, 22.0, 13.9
3h	4.00(s, 2H), 3.60(q, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.67(d, 1H), 1.55(s, 5H), 1.37(s, 2H), 1.26(d, 10H), 0.86(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 31.2, 28.6, 28.6, 28.1, 28.1, 25.4, 24.2, 22.0, 13.9
3i	4.00(s, 2H), 3.60(q, 1H), 3.17(d, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(d, 1H), 1.66(q, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.26(t, 12H), 0.86(s, 3H)	172.7, 63.6, 56.0, 39.8, 38.0, 34.0, 33.3, 31.2, 28.8, 28.6, 28.6, 28.1, 28.0, 25.3, 24.2, 22.0, 13.9
3j	3.99(s, 2H), 3.60(q, 1H), 3.17(s, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(d, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 14H), 0.85(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.2, 28.9, 28.9, 28.6, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3k	3.99(s, 2H), 3.59(t, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.40(t, 1H), 2.28(s, 2H), 1.86(t, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 16H), 0.85(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.3, 29.0, 28.9, 28.9, 28.7, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3l	3.99(s, 2H), 3.59(q, 1H), 3.17(q, 1H), 3.12(s, 1H), 2.40(t, 1H), 2.28(s, 2H), 1.86(t, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 18H), 0.85(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.3, 29.0, 29.0, 28.9, 28.9, 28.7, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3m	7.42(t, 2H), 7.26(s, 1H), 7.12(t, 2H), 3.65(q, 1H), 3.20(d, 1H), 3.12(t, 1H), 2.59(s, 2H), 2.43(d, 1H), 1.90(t, 1H), 1.67(d, 4H), 1.48(d, 2H)	171.7, 150.5, 129.4, 129.4, 125.7, 121.8, 121.8, 56.0, 39.9, 38.1, 34.0, 33.3, 28.0, 24.1
Compd.	¹H NMR(600 MHz), δ	¹³C NMR(150 MHz), δ
3n	7.36(d, 5H), 5.09(s, 2H), 3.59(q, 1H), 3.16(s, 1H), 3.10(t, 1H), 2.36(t, 3H), 1.84(q, 1H), 1.64(d, 1H), 1.56(q, 3H), 1.37(s, 2H)	172.6, 136.2, 128.4, 128.4, 127.9, 127.9, 127.9, 65.3, 56.0, 39.8, 38.1, 34.0, 33.3, 28.0, 24.2
3o	7.69(s, 1H), 6.50(d, 1H), 6.45(d, 1H), 5.04(s, 2H), 3.59(s, 1H), 3.17(d, 1H), 3.11(q, 1H), 2.39(d, 1H), 2.32(s, 2H), 1.85(q, 1H), 1.64(q, 1H), 1.54(s, 3H), 1.35(s, 2H)	172.4, 149.4, 143.6, 110.7, 110.7, 57.3, 56.0, 39.8, 38.1, 33.9, 33.1, 27.9, 24.1
3p	7.55(q, 1H), 7.16(d, 1H), 7.01(q, 1H), 5.25(s, 2H), 3.58(s, 1H), 3.16(s, 1H), 3.10(d, 1H), 2.39(s, 1H), 2.33(s, 2H), 1.84(t, 1H), 1.64(s, 1H), 1.55(s, 3H), 1.35(d, 2H)	172.5, 138.1, 128.3, 127.3, 126.8, 59.8, 56.0, 39.8, 38.1, 33.9, 33.2, 28.0, 24.2
3q	8.54(s, 1H), 7.81(s, 1H), 7.39(d, 1H), 7.33(s, 1H), 5.15(s, 2H), 3.61(s, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.42(s, 3H), 1.87(t, 1H), 1.58(s, 1H), 1.40(s, 3H), 1.23(s, 2H)	172.5, 155.7, 149.1, 136.9, 122.9, 121.5, 66.0, 56.0, 39.8, 38.1, 34.0, 33.2, 28.0, 24.1
3r	8.47(s, 1H), 8.22(d, 1H), 6.52(d, 1H), 3.62(d, 1H), 3.19(d, 1H), 3.12(t, 1H), 2.57(t, 2H), 2.42(q, 1H), 1.89(q, 1H), 1.70(s, 1H), 1.59—1.65(m, 3H), 1.47(q, 2H)	171.4, 170.1, 156.8, 149.7, 141.0, 116.8, 56.0, 39.8, 38.1, 34.0, 32.6, 27.8, 24.1
3s	8.07(d, 1H), 7.77(d, 1H), 7.27(s, 1H), 7.15(d, 1H), 6.48(d, 1H), 3.66(s, 1H), 3.19(s, 1H), 3.14(s, 1H), 2.63(s, 2H), 2.43(d, 1H), 1.90(d, 1H), 1.69(t, 3H), 1.61(s, 1H), 1.48(d, 2H)	171.3, 159.7, 154.1, 152.9, 143.8, 129.3, 118.6, 116.6, 115.5, 110.0, 56.0, 39.9, 38.1, 34.0, 33.3, 27.9, 23.9
3t	9.98(s, 1H), 7.58(d, 2H), 7.03(d, 2H), 3.65(q, 1H), 3.19(d, 1H), 3.12(d, 1H), 2.56(t, 2H), 2.43(d, 1H), 2.03(s, 3H), 1.89(d, 1H), 1.60—1.71(m, 4H), 1.46(d, 2H)	171.8, 168.2, 145.6, 136.9, 121.8, 121.8, 119.8, 119.8, 56.0, 39.9, 38.1, 34.0, 33.2, 28.0, 25.3, 24.1
3u	4.79(s, 1H), 3.60(q, 1H), 3.18(d, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.24(s, 2H), 1.87(t, 2H), 1.63(q, 3H), 1.53(s, 3H), 1.36(s, 2H), 1.30(d, 1H), 1.06(s, 1H), 0.91(d, 6H), 0.87(d, 3H), 0.81(t, 2H)	172.2, 70.0, 56.0, 46.9, 43.6, 40.0, 39.9, 38.1, 34.0, 33.6, 32.7, 31.8, 28.0, 26.5, 25.2, 24.3, 22.1
3v	7.07(d, 2H), 6.77(d, 2H), 5.23(s, 1H), 4.24—4.27(m, 2H), 3.52(t, 1H), 3.17(t, 1H), 3.11(t, 1H), 2.86(s, 2H), 2.45(d, 1H), 2.29(d, 2H), 1.89(t, 1H), 1.63(q, 4H), 1.42(s, 1H), 1.38(s, 1H)	173.7, 154.4, 130.0, 130.0, 129.7, 115.4, 115.4, 65.1, 56.4, 40.2, 38.4, 34.5, 34.2, 34.1, 28.7, 24.6
3w	8.74(s, 1H), 8.68(s, 1H), 6.63(d, 1H), 6.60(d, 1H), 6.46(q, 1H), 4.12(s, 2H), 3.59(q, 1H), 3.17(s, 1H), 3.11(t, 1H), 2.68(s, 2H), 2.40(d, 1H), 2.27(s, 2H), 1.86(t, 1H), 1.63(d, 1H), 1.51(d, 3H), 1.34(t, 2H)	172.7, 145.0, 143.7, 128.5, 119.4, 116.1, 115.4, 64.6, 56.0, 40.1, 38.1, 34.0, 33.8, 33.4, 28.0, 24.2

Compd.	¹H NMR(600 MHz), δ	¹³C NMR(150 MHz), δ
3a	3.61(q, 2H), 3.57(s, 3H), 3.18(t, 1H), 3.12(q, 1H), 2.41(d, 1H), 2.31(s, 2H), 1.87(q, 1H), 1.66(s, 1H), 1.54(d, 2H), 1.37(d, 2H)	172.8, 56.0, 51.1, 39.9, 38.1, 34.0, 33.1, 28.1, 24.2
3b	4.05(d, 2H), 3.61(q, 1H), 3.18(s, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.28(s, 2H), 1.86(q, 1H), 1.66(s, 1H), 1.54(d, 2H), 1.37(d, 2H), 1.23(s, 1H), 1.17(s, 3H)	172.8, 59.6, 56.0, 39.9, 38.1, 34.0, 33.3, 28.0, 24.2, 14.1
3c	3.96(s, 2H), 3.61(q, 1H), 3.18(q, 1H), 3.12(q, 1H), 2.41(d, 1H), 2.30(s, 2H), 1.86(q, 1H), 1.67(d, 1H), 1.57(s, 5H), 1.38(d, 2H), 0.88(s, 3H)	172.8, 65.1, 56.0, 39.9, 38.1, 34.0, 33.3, 28.1, 24.2, 21.5, 10.2
3d	4.01(s, 2H), 3.60(q, 1H), 3.18(d, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.66(s, 1H), 1.54(s, 5H), 1.33(t, 4H), 0.88(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 30.2, 28.1, 24.2, 18.6, 13.5
3e	4.00(s, 2H), 3.60(q, 1H), 3.18(d, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.66(s, 1H), 1.55(d, 5H), 1.37(s, 2H), 1.29(d, 4H), 0.87(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 28.1, 27.8, 27.6, 24.2, 21.7, 13.8
3f	4.00(s, 2H), 3.60(q, 1H), 3.18(t, 1H), 3.11(t, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(q, 1H), 1.66(s, 1H), 1.55(s, 5H), 1.37(d, 2H), 1.27(s, 6H), 0.86(s, 3H)	172.8, 63.7, 56.0, 39.9, 38.1, 34.0, 33.3, 30.8, 28.1, 28.1, 25.0, 24.2, 22.0, 13.8
3g	4.00(s, 2H), 3.60(t, 1H), 3.17(s, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(q, 1H), 1.66(t, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.26(d, 8H), 0.86(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 31.1, 28.3, 28.1, 28.0, 25.3, 24.2, 22.0, 13.9
3h	4.00(s, 2H), 3.60(q, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(t, 1H), 1.67(d, 1H), 1.55(s, 5H), 1.37(s, 2H), 1.26(d, 10H), 0.86(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.3, 31.2, 28.6, 28.6, 28.1, 28.1, 25.4, 24.2, 22.0, 13.9
3i	4.00(s, 2H), 3.60(q, 1H), 3.17(d, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.87(d, 1H), 1.66(q, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.26(t, 12H), 0.86(s, 3H)	172.7, 63.6, 56.0, 39.8, 38.0, 34.0, 33.3, 31.2, 28.8, 28.6, 28.6, 28.1, 28.0, 25.3, 24.2, 22.0, 13.9
3j	3.99(s, 2H), 3.60(q, 1H), 3.17(s, 1H), 3.12(s, 1H), 2.41(d, 1H), 2.29(s, 2H), 1.86(d, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 14H), 0.85(s, 3H)	172.8, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.2, 28.9, 28.9, 28.6, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3k	3.99(s, 2H), 3.59(t, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.40(t, 1H), 2.28(s, 2H), 1.86(t, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 16H), 0.85(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.3, 29.0, 28.9, 28.9, 28.7, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3l	3.99(s, 2H), 3.59(q, 1H), 3.17(q, 1H), 3.12(s, 1H), 2.40(t, 1H), 2.28(s, 2H), 1.86(t, 1H), 1.66(s, 1H), 1.54(d, 5H), 1.37(d, 2H), 1.24(s, 18H), 0.85(s, 3H)	172.7, 63.6, 56.0, 39.9, 38.1, 34.0, 33.4, 31.3, 29.0, 29.0, 28.9, 28.9, 28.7, 28.6, 28.1, 28.1, 25.4, 24.3, 22.1, 13.9
3m	7.42(t, 2H), 7.26(s, 1H), 7.12(t, 2H), 3.65(q, 1H), 3.20(d, 1H), 3.12(t, 1H), 2.59(s, 2H), 2.43(d, 1H), 1.90(t, 1H), 1.67(d, 4H), 1.48(d, 2H)	171.7, 150.5, 129.4, 129.4, 125.7, 121.8, 121.8, 56.0, 39.9, 38.1, 34.0, 33.3, 28.0, 24.1
Compd.	¹H NMR(600 MHz), δ	¹³C NMR(150 MHz), δ
3n	7.36(d, 5H), 5.09(s, 2H), 3.59(q, 1H), 3.16(s, 1H), 3.10(t, 1H), 2.36(t, 3H), 1.84(q, 1H), 1.64(d, 1H), 1.56(q, 3H), 1.37(s, 2H)	172.6, 136.2, 128.4, 128.4, 127.9, 127.9, 127.9, 65.3, 56.0, 39.8, 38.1, 34.0, 33.3, 28.0, 24.2
3o	7.69(s, 1H), 6.50(d, 1H), 6.45(d, 1H), 5.04(s, 2H), 3.59(s, 1H), 3.17(d, 1H), 3.11(q, 1H), 2.39(d, 1H), 2.32(s, 2H), 1.85(q, 1H), 1.64(q, 1H), 1.54(s, 3H), 1.35(s, 2H)	172.4, 149.4, 143.6, 110.7, 110.7, 57.3, 56.0, 39.8, 38.1, 33.9, 33.1, 27.9, 24.1
3p	7.55(q, 1H), 7.16(d, 1H), 7.01(q, 1H), 5.25(s, 2H), 3.58(s, 1H), 3.16(s, 1H), 3.10(d, 1H), 2.39(s, 1H), 2.33(s, 2H), 1.84(t, 1H), 1.64(s, 1H), 1.55(s, 3H), 1.35(d, 2H)	172.5, 138.1, 128.3, 127.3, 126.8, 59.8, 56.0, 39.8, 38.1, 33.9, 33.2, 28.0, 24.2
3q	8.54(s, 1H), 7.81(s, 1H), 7.39(d, 1H), 7.33(s, 1H), 5.15(s, 2H), 3.61(s, 1H), 3.17(s, 1H), 3.11(d, 1H), 2.42(s, 3H), 1.87(t, 1H), 1.58(s, 1H), 1.40(s, 3H), 1.23(s, 2H)	172.5, 155.7, 149.1, 136.9, 122.9, 121.5, 66.0, 56.0, 39.8, 38.1, 34.0, 33.2, 28.0, 24.1
3r	8.47(s, 1H), 8.22(d, 1H), 6.52(d, 1H), 3.62(d, 1H), 3.19(d, 1H), 3.12(t, 1H), 2.57(t, 2H), 2.42(q, 1H), 1.89(q, 1H), 1.70(s, 1H), 1.59—1.65(m, 3H), 1.47(q, 2H)	171.4, 170.1, 156.8, 149.7, 141.0, 116.8, 56.0, 39.8, 38.1, 34.0, 32.6, 27.8, 24.1
3s	8.07(d, 1H), 7.77(d, 1H), 7.27(s, 1H), 7.15(d, 1H), 6.48(d, 1H), 3.66(s, 1H), 3.19(s, 1H), 3.14(s, 1H), 2.63(s, 2H), 2.43(d, 1H), 1.90(d, 1H), 1.69(t, 3H), 1.61(s, 1H), 1.48(d, 2H)	171.3, 159.7, 154.1, 152.9, 143.8, 129.3, 118.6, 116.6, 115.5, 110.0, 56.0, 39.9, 38.1, 34.0, 33.3, 27.9, 23.9
3t	9.98(s, 1H), 7.58(d, 2H), 7.03(d, 2H), 3.65(q, 1H), 3.19(d, 1H), 3.12(d, 1H), 2.56(t, 2H), 2.43(d, 1H), 2.03(s, 3H), 1.89(d, 1H), 1.60—1.71(m, 4H), 1.46(d, 2H)	171.8, 168.2, 145.6, 136.9, 121.8, 121.8, 119.8, 119.8, 56.0, 39.9, 38.1, 34.0, 33.2, 28.0, 25.3, 24.1
3u	4.79(s, 1H), 3.60(q, 1H), 3.18(d, 1H), 3.11(d, 1H), 2.41(d, 1H), 2.24(s, 2H), 1.87(t, 2H), 1.63(q, 3H), 1.53(s, 3H), 1.36(s, 2H), 1.30(d, 1H), 1.06(s, 1H), 0.91(d, 6H), 0.87(d, 3H), 0.81(t, 2H)	172.2, 70.0, 56.0, 46.9, 43.6, 40.0, 39.9, 38.1, 34.0, 33.6, 32.7, 31.8, 28.0, 26.5, 25.2, 24.3, 22.1
3v	7.07(d, 2H), 6.77(d, 2H), 5.23(s, 1H), 4.24—4.27(m, 2H), 3.52(t, 1H), 3.17(t, 1H), 3.11(t, 1H), 2.86(s, 2H), 2.45(d, 1H), 2.29(d, 2H), 1.89(t, 1H), 1.63(q, 4H), 1.42(s, 1H), 1.38(s, 1H)	173.7, 154.4, 130.0, 130.0, 129.7, 115.4, 115.4, 65.1, 56.4, 40.2, 38.4, 34.5, 34.2, 34.1, 28.7, 24.6
3w	8.74(s, 1H), 8.68(s, 1H), 6.63(d, 1H), 6.60(d, 1H), 6.46(q, 1H), 4.12(s, 2H), 3.59(q, 1H), 3.17(s, 1H), 3.11(t, 1H), 2.68(s, 2H), 2.40(d, 1H), 2.27(s, 2H), 1.86(t, 1H), 1.63(d, 1H), 1.51(d, 3H), 1.34(t, 2H)	172.7, 145.0, 143.7, 128.5, 119.4, 116.1, 115.4, 64.6, 56.0, 40.1, 38.1, 34.0, 33.8, 33.4, 28.0, 24.2

Compd.	Scavenging ratio(%)			Compd.	Scavenging ratio(%)
Compd.	1 h	2 h	3 h	Compd.	1 h	2 h	3 h
3a	66.8±0.9	86.6±1.0	96.6±0.9	3n	48.0±0.5	58.9±0.8	63.9±1.1
3b	67.0±0.6	77.8±0.9	88.2±1.2	3o	53.1±0.4	61.9±0.9	71.8±0.8
3c	37.1±1.4	48.9±1.4	58.9±1.5	3p	53.9±0.6	63.7±0.7	68.2±0.9
3d	42.5±1.7	55.2±1.6	72.5±1.4	3q	45.3±0.6	57.5±0.8	82.5±1.4
3e	76.0±1.9	84.1±1.7	90.0±1.9	3r	52.5±0.4	65.9±0.7	77.5±0.7
3f	55.3±0.9	76.3±1.7	87.3±1.8	3s	50.0±0.5	62.5±0.6	72.5±0.8
3g	45.9±1.4	58.9±1.3	68.4±1.7	3t	48.9±0.4	68.7±0.7	76.9±1.1
3h	37.7±0.6	53.8±1.6	58.7±1.4	3u	57.5±0.5	72.5±0.8	77.5±1.4
3i	47.0±0.7	52.5±0.6	57.5±1.1	3v	74.8±0.3	84.9±0.8	93.1±1.0
3j	42.9±0.4	66.6±1.4	74.1±1.5	3w	58.1±0.4	74.9±0.7	82.4±0.8
3k	61.9±0.7	70.6±0.9	82.5±1.4	Lipoic acid	25.7±0.2	47.5±0.7	57.5±0.8
3l	42.5±0.9	57.5±1.1	72.5±1.3	Carnosine	79.2±1.4	89.6±1.0	96.2±1.1
3m	37.5±0.5	57.5±1.4	82.5±1.2	GSH	90.0±0.7	100.0±0.5	100.0±0.3

硫辛酸酯类衍生物的合成及生物活性

Synthesis and Biological Activity of Lipoic Acid Ester Derivatives^†

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 9

参考文献 33

相关文章 15

编辑推荐

Metrics

本文评价

Compd.	Scavenging ratio(%)	Compd.	Scavenging ratio(%)	Compd.	Scavenging ratio(%)
3a	5.9±0.3	3j	31.6±0.4	3s	29.6±0.9
3b	9.4±0.1	3k	11.7±0.1	3t	36.7±0.1
3c	35.2±1.3	3l	10.5±0.5	3u	26.0±0.4
3d	28.1±1.3	3m	31.9±1.3	3v	58.2±0.9
3e	28.7±0.8	3n	8.1±0.1	3w	64.9±0.4
3f	45.4±0.4	3o	54.0±1.3	Lipoic acid	80.0±0.5
3g	38.2±0.4	3p	51.3±0.4	Vitamin C	80.0±0.9
3h	18.5±0.8	3q	16.4±1.1	Trolox	79.7±0.1
3i	22.1±0.4	3r	34.3±0.9

Compd.	Scavenging ratio(%)	Compd.	Scavenging ratio(%)	Compd.	Scavenging ratio(%)
3a	31.3±1.3	3j	31.1±0.4	3s	23.9±0.4
3b	61.4±3.0	3k	31.6±0.1	3t	24.7±0.1
3c	47.2±2.4	3l	29.7±0.4	3u	61.3±0.1
3d	36.9±0.2	3m	26.9±0.2	3v	73.8±1.3
3e	52.8±1.9	3n	23.9±1.3	3w	99.3±0.3
3f	28.7±0.4	3o	47.6±0.2	Lipoic acid	39.4±0.2
3g	32.6±0.3	3p	39.3±0.7	Vitamin C	99.9±0.3
3h	29.8±0.1	3q	27.6±1.2	Trolox	99.9±0.1
3i	39.9±1.0	3r	39.7±1.1

Compd.	FRAP/(mmol·g^-1)	Compd.	FRAP/(mmol·g^-1)	Compd.	FRAP/(mmol·g^-1)
3a	27.8±0.2	3j	19.3±0.2	3s	11.9±0.3
3b	32.5±0.8	3k	16.4±0.3	3t	10.9±0.2
3c	12.6±0.5	3l	19.9±0.8	3u	23.4±0.4
3d	9.7±0.2	3m	23.1±1.2	3v	30.9±0.5
3e	16.1±0.2	3n	17.5±0.3	3w	216.4±0.4
3f	19.3±0.3	3o	17.0±0.1	Lipoic acid	16.3±0.1
3g	14.3±0.2	3p	19.9±0.3	Vitamin C	205.1±1.7
3h	20.1±0.9	3q	17.1±0.1	Trolox	209.2±0.6
3i	23.4±0.3	3r	15.1±0.3

Compd.	Scavenging ratio(%)	Compd.	Scavenging ratio(%)	Compd.	Scavenging ratio(%)
3a	19.6±0.4	3j	40.5±1.7	3r	20.0±0.3
3b	18.7±0.6	3k	18.7±0.6	3s	13.4±0.6
3c	17.5±0.9	3l	19.3±0.9	3t	34.7±1.4
3d	24.1±1.0	3m	32.0±1.5	3u	24.9±1.0
3e	14.0±0.2	3n	32.1±1.4	3v	12.7±0.7
3f	7.9±0.2	3o	8.5±0.4	3w	99.9±2.1
3g	22.7±1.2	3p	15.5±0.5	Lipoic acid	39.4±1.2
3h	18.7±1.1	3q	33.4±0.9	Trolox	95.6±0.3
3i	10.2±0.3

Compd.	Remaining after 2h incubation(%)	Compd.	Remaining after 2 h incubation(%)	Compd.	Remaining after 2 h incubation(%)
3a	96.5±0.2	3i	97.3±0.3	3q	97.4±0.3
3b	97.1±0.3	3j	98.9±0.2	3r	98.4±0.1
3c	97.5±0.2	3k	98.7±0.3	3s	97.7±0.2
3d	98.8±0.1	3l	98.3±0.2	3t	98.3±0.2
3e	98.2±0.2	3m	97.1±0.3	3u	98.7±0.3
3f	97.3±0.1	3n	96.8±0.2	3v	98.5±0.1
3g	97.9±0.1	3o	98.7±0.2	3w	98.0±0.2
3h	96.7±0.2	3p	98.6±0.3	Lipoic acid	4.8±0.1

[1]	黄罗仪, 翁约约, 黄旭慧, 王朝杰. 车前草中黄酮类成分结构和性质的理论研究[J]. 高等学校化学学报, 2021, 42(9): 2752.
[2]	胡皓程, 李文利, 张嘉宁, 刘宇博. 黑木耳寡糖的提取、结构表征及生物活性[J]. 高等学校化学学报, 2021, 42(8): 2465.
[3]	王雁冰, 张辉, 杨峻山, 陈炳鹏, 孙佳明. 破骨风中木脂素类化合物的分离鉴定及抗氧化活性[J]. 高等学校化学学报, 2018, 39(9): 1942.
[4]	练小卫, 黄净净, 陶朱, 周清娣, 张前军, 卫钢. 八元瓜环与乔松素的主客体作用及对乔松素性质的影响[J]. 高等学校化学学报, 2018, 39(2): 226.
[5]	黄净净, 许志玲, 练小卫, 张晓东, 陶朱, 周清娣, 张前军, 卫钢. 八元瓜环与黄岑苷的主客体相互作用及对黄岑苷性质的影响[J]. 高等学校化学学报, 2018, 39(11): 2425.
[6]	杨昕, 张迪, 宋立敏, 许茜, 许卉, 刘珂. 基于光谱分析的姜黄素碱性自氧化及其产物的抗氧化活性[J]. 高等学校化学学报, 2017, 38(9): 1549.
[7]	李梦杰, 练小卫, 许志玲, 邢旭阳, 张建新, 李瑞, 陶朱, 张前军. 七元瓜环对2'-羟基查尔酮溶解性、稳定性及抗氧化活性的影响[J]. 高等学校化学学报, 2017, 38(3): 442.
[8]	刘洋, 殷璐, 龚桂萍, 彭艺芳, 黄琳娟, 王仲孚. 黑果枸杞叶多糖LRLP3的结构、抗氧化活性及免疫活性[J]. 高等学校化学学报, 2016, 37(2): 261.
[9]	徐燕, 田沙沙, 俞和, 杨文智, 朱华结. 棘孢曲霉中分离的2个新化合物[J]. 高等学校化学学报, 2015, 36(6): 1107.
[10]	臧皓, 孙佳明, 黄晓光, 纪扬, 代婷婷, 高晓晨, 李晓东, 张辉. N-取代肌肽酰胺类衍生物的合成及生物活性[J]. 高等学校化学学报, 2014, 35(12): 2567.
[11]	杨树平, 韩立军, 潘燕, 王大奇, 王南南, 王婷. 8-或6-(3-氯苯甲酰)香豆素衍生物的合成、表征、生物活性及与牛血清白蛋白的相互作用[J]. 高等学校化学学报, 2013, 34(2): 364.
[12]	邹险峰, 吕绍武. 具有谷胱甘肽过氧化物酶(GPx)活力的含硒四肽(SecRGD)[J]. 高等学校化学学报, 2012, 33(05): 983.
[13]	黄晓纯, 郑军生, 陈填烽, 张逸波, 罗懿, 郑文杰. 1,2,5-硒二唑嘧啶衍生物ASPO的合成及抗氧化与抗肿瘤活性[J]. 高等学校化学学报, 2012, 33(05): 976.
[14]	韩璐杜立波贾宏瑛田秋刘扬. 新型Trolox-壳聚糖纳米颗粒的制备及抗氧化效应[J]. 高等学校化学学报, 2011, 32(5): 1013.
[15]	张培全1, 曾和平2. 乙烯基桥联的8-羟基喹啉衍生物的合成、抗氧化活性及促进鼠骨髓间质干细胞增殖的研究[J]. 高等学校化学学报, 2010, 31(1): 74.

硫辛酸酯类衍生物的合成及生物活性

Synthesis and Biological Activity of Lipoic Acid Ester Derivatives†

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 9

参考文献 33

相关文章 15

编辑推荐

Metrics

本文评价

Synthesis and Biological Activity of Lipoic Acid Ester Derivatives^†