Page 204 - 《精细化工》2023年第11期

第 40 卷第 11 期 精 细 化 工 Vol.40, No.11
2 023 年 11 月 FINE CHEMICALS Nov. 2023

医药与日化原料
含氨基酸结构的磺酰胺衍生物合成与生物活性

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董向涛，杨昊楠，卢子聪，杨家强
（遵义医科大学 药学院，贵州 遵义 563000）

摘要：采用分子杂交策略设计合成了 15 个氨基酸结构的磺酰胺衍生物，对其进行了抗菌活性评价。首先，苯磺
酰氯与氨基酸反应制得了苯磺酰氨基酸（中间体Ⅰ）；然后，以芳香醛、亚磷酸酯、乙酸铵和三氟甲磺酸铝为
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原料，一锅法制得了 α-氨基膦酸酯（中间体Ⅱ）；最后，中间体Ⅰ与Ⅱ缩合制得目标物。经 HNMR、 CNMR
和 MS 确认结构。结果表明，该类化合物对大肠杆菌（E. coli）和耐氟喹诺酮大肠杆菌（FREC）活性最为显著。
其中，化合物Ⅲb〔{(2-氟苯基)[2-(苯基磺酰氨基)苯丙酰氨基]甲基}膦酸二乙酯〕、Ⅲc〔{(4-氟苯基)[2-(苯基磺
酰氨基)苯丙酰氨基]甲基}膦酸二乙酯〕、Ⅲh〔{(2-氟苯基)[2-(苯基磺酰氨基)异戊酰氨基]甲基}膦酸二乙酯〕和
Ⅲm〔{(苯基)[2-(苯基磺酰氨基)乙酰氨基]甲基}膦酸二乙酯〕对 E. coli 的最小抑菌质量浓度（MIC）均为 16 μg/L，
化合物Ⅲn〔{(2-氟苯基)[2-(苯基磺酰氨基)乙酰氨基]甲基}膦酸二乙酯〕对 E. coli 的 MIC 为 8 μg/L，抗菌活性不
低于对照药苯唑西林；化合物Ⅲb、Ⅲh、Ⅲm 和Ⅲn 对 FREC 的 MIC 分别为 32、32、32 和 16 μg/L，优于对照
药苯唑西林和诺氟沙星。
关键词：磺酰胺；氨基酸；膦酸酯；合成；抗菌活性；医药原料
中图分类号：R914.5；TQ463+.42 文献标识码：A 文章编号：1003-5214 (2023) 11-2516-06

Synthesis and biological activities of sulfonamide derivatives
containing amino acid moiety

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DONG Xiangtao, YANG Haonan, LU Zicong, YANG Jiaqiang
（School of Pharmacy, Zunyi Medical University, Zunyi 563000, Guizhou, China）

Abstract: Fifteen sulfonamide derivatives containing amino acid moiety were designed and synthesized by
molecular hybridization strategy, and evaluated for their antibacterial activity. Specifically, benzenesulfonyl
amino acids (intermediate Ⅰ) was firstly prepared from reaction of benzenesulfonyl chloride and amino acids.
α-Aminophosphonates (intermediate Ⅱ) were then synthesized from one pot reaction of aromatic aldehyde,
phosphite, ammonium acetate and aluminum trifluoromethanesulfonate. Finally, the target products were
obtained by condensation reaction of intermediate Ⅰ and Ⅱ. The structures of the target products obtained
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were confirmed by HNMR, CNMR and MS. The results showed that these compounds exhibited the most
significant activities against Escherichia coli (E. coli) and fluoroquinolone-resistant Escherichia coli (FREC).
Among them, the MIC of Ⅲb (diethyl{(2-fluorophenyl) [2-(phenylsulfonylamino)phenylpropanylamino]
methyl}phosphonate), Ⅲc (diethyl{(4-fluorophenyl)[2-(phenylsulfonylamino)phenylpropanylamino]methyl}
phosphonate), Ⅲh (diethyl{(2-fluorophenyl)[2-(phenylsulfonylamino)isovalerylamino]methyl}phosphonate)
and Ⅲm (diethyl{(phenyl)[2-(phenylsulfonyl amino)acetamido]methyl}phosphonate) displayed a MIC to
E. coli of 16 μg/L, while Ⅲn (diethyl{(2-fluorophenyl)[2-(phenylsulfonylamino)acetamido]methyl}phosphonate)
showed a MIC against E. coli of 8 μg/L, which were no less effective when compared with control drug
Oxacillin. The MIC of Ⅲb, Ⅲh, Ⅲm and Ⅲn against FREC were 32, 32, 32 and 16 μg/L, respectively,
which were superior to those of control drugs Oxacillin and Norfloxacin.
Key words: sulfonamides; amino acids; phosphonates; synthesis; antibacterial activities; drug materials

收稿日期：2023-01-17; 定用日期：2023-03-14; DOI: 10.13550/j.jxhg.20230033
基金项目：贵州省卫生健康委科学技术基金项目（gzwkj2021-444）
作者简介：董向涛（1999—），男，硕士生。联系人：杨家强（1979—），男，教授，E-mail: yjqcn@126.com。