大黄酰氨基酰胺类衍生物的合成及其抗菌活性

doi:10.3969/j.issn.0253-2417.2023.04.007

林产化学与工业 ›› 2023, Vol. 43 ›› Issue (4): 47-52.doi: 10.3969/j.issn.0253-2417.2023.04.007

大黄酰氨基酰胺类衍生物的合成及其抗菌活性

廖鹏¹^,², 周灿¹^,², 刘静姿³, 于慧斌¹^,², 赵利军¹^,²^,*()

1. 十堰市人民医院湖北医药学院附属人民医院药学部, 湖北十堰 442000
2. 武当特色中药研究湖北省重点实验室(湖北医药学院), 湖北十堰 442000
3. 贵州医科大学药学院, 贵州贵阳 550004

收稿日期:2022-05-14 出版日期:2023-08-28 发布日期:2023-08-26
通讯作者: 赵利军 E-mail:791511650@qq.com
作者简介:赵利军，副主任药师，硕士，主要从事中药化学研究；E-mail: 791511650@qq.com
廖鹏(1992—)，男，湖北十堰人，主管药师，硕士，主要从事药物制剂研究
基金资助:
贵州省科技厅资助项目(黔科合SY字[2012]3103);贵州省教育厅资助项目([黔省专合字2012]89号)

Synthesis and Antibacterial Activity of Rhein Amidoamide Derivatives

Peng LIAO¹^,², Can ZHOU¹^,², Jingzi LIU³, Huibin YU¹^,², Lijun ZHAO¹^,²^,*()

1. Department of Pharmacy, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, China
2. Hubei Key Laboratory of Wudang Local Chinese Medicine Research(Hubei University of Medicine), Shiyan 442000, China
3. School of Pharmacy, Guizhou Medical University, Guiyang 550004, China

Received:2022-05-14 Online:2023-08-28 Published:2023-08-26
Contact: Lijun ZHAO E-mail:791511650@qq.com

摘要/Abstract

摘要：

为改善大黄酸的理化性质及抗菌活性，对大黄酸结构进行改造。以大黄酸为原料，苯并三氮唑-N, N, N', N'-四甲基脲六氟磷酸酯(HBTU)为缩合剂、N, N-二异丙基乙胺(DIPEA)为催化剂，分别与L-脯氨酸甲酯盐酸盐、L-色氨酸甲酯盐酸盐和L-苯丙氨酸甲酯盐酸盐反应，再加入取代苄胺，合成了6个目标化合物4a~4f。利用核磁共振(¹H NMR、¹³C NMR、¹⁹F NMR)及高分辨质谱对目标化合物结构进行确证和表征，并首次探讨了该类化合物对大肠埃希菌、金黄色葡萄球菌、普通变形杆菌的抑菌活性。研究结果表明：部分目标化合物具有较好的抑菌活性，其中化合物4a对金黄色葡萄球菌的最低抑制质量浓度(MIC)值为0.78 mg/L，化合物4e对普通变形杆菌的MIC值为0.39 mg/L，抑菌活性优于大黄酸，甚至优于对照药物氨苄西林。

关键词: 大黄酸, 氨基酸, 取代苄胺, 抗菌

Abstract:

In order to improve the physicochemical properties and antibacterial activity of rhein, its structure was modified. Using O-benzotriazole-N, N, N′, N′-tetramethylurea(HBTU) as condensing agent, and N, N-diisopropylethylamine(DIPEA) as catalyst, six target compounds (4a-4f) were synthesized by the reaction of rhein with L-proline methyl ester hydrochloride, L-tryptophan methyl ester hydrochloride, L-phenylalanine methyl ester hydrochloride and substituted benzylamine. The structures of the target compounds were confirmed and characterized by(¹H, ¹³C, ¹⁹F) NMR and high-resolution mass spectrometry. The antibacterial activities of these compounds against Escherichia coli, Staphylococcus aureus and Proteus vulgaris were tested for the first time. The results indicated that some of the target compounds had good antibacterial activities, and the minimum inhibitory concentration(MIC) value of compound 4a against S. aureus was 0.78 mg/L, and the MIC value of compound 4e against P. vulgaris was 0.39 mg/L. Their antibacterial activities were better than that of rhein and even better than that of the control drug ampicillin.

Key words: rhein, amino acid, substitute benzylamine, antibacterial

中图分类号:

TQ35
R914.5

廖鹏, 周灿, 刘静姿, 于慧斌, 赵利军. 大黄酰氨基酰胺类衍生物的合成及其抗菌活性[J]. 林产化学与工业, 2023, 43(4): 47-52.

Peng LIAO, Can ZHOU, Jingzi LIU, Huibin YU, Lijun ZHAO. Synthesis and Antibacterial Activity of Rhein Amidoamide Derivatives[J]. Chemistry and Industry of Forest Products, 2023, 43(4): 47-52.

图/表 2

参考文献 23

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化合物 compound	MIC/(mg·L^-1)
化合物 compound	E. coli	S. aureus	P. vulgaris
4a	1.56	0.78	3.13
4b	3.13	1.56	3.13
4c	6.25	12.50	12.50
4d	25.00	25.00	6.25
4e	1.56	3.13	0.39
4f	1.56	6.25	0.78
大黄酸rhein	3.13	3.13	1.56
氨苄西林ampicillin	0.78	1.56	0.78
空白对照control	—	—	—

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大黄酰氨基酰胺类衍生物的合成及其抗菌活性

Synthesis and Antibacterial Activity of Rhein Amidoamide Derivatives

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