含长链烷基吡啶盐氯胺的合成及抗菌性能  

Synthesis and antibacterial properties of long-chain pyridinium N-chloramines

作　　者：李令东[1,2] 刘鹏飞[2] 张维伦 张颂伟 贾冬雪 周豪[2] LI Lingdong;LIU Pengfei;ZHANG Weilun;ZHANG Songwei;JIA Dongxue;ZHOU Hao(State Key Laboratory of Fine Chemicals,Dalian University of Technology,Panjin 124221,Liaoning,China;School of Chemical Engineering and Ocean&Life Science,Dalian University of Technology,Panjin 124221,Liaoning,China)

机构地区：[1]大连理工大学精细化工国家重点实验室,辽宁盘锦124221 [2]大连理工大学化工海洋与生命学院,辽宁盘锦124221

出　　处：《精细化工》2025年第1期149-158,共10页Fine Chemicals

基　　金：国家自然科学基金项目(41977197)。

摘　　要：以4-羟基吡啶为连接单元,通过多步合成,制备了O-烷基化衍生的长链烷基吡啶盐氯胺和N-烷基化衍生的长链烷基吡啶盐氯胺,经NMR和HRMS确证了前体和氯胺结构。以金黄色葡萄球菌和大肠杆菌为模式菌株,以已报道的氯胺1-[3-(4,4-二甲基-3-氯-2,5-二氧代咪唑烷-1-基)丙基]吡啶-1-氯化物(Ⅱb)为对照,对所合成的氯胺进行了初步抗菌测试。结果表明,对位衍生吡啶盐氯胺抗菌活性明显优于间位衍生氯胺对应物,且抗菌活性随着烷基链(—C_(6)H_(13)、—C_(8)H_(17)、—C_(10)H_(2)1、—C_(12)H_(2)5)的增长而显著增强;N-烷基化衍生的长链烷基吡啶盐氯胺的抗菌性能明显优于O-烷基化衍生的长链烷基吡啶盐氯胺。携有—C_(12)H_(25)链的吡啶季铵盐氯胺4-正十二烷氧基-1-[3-(4,4-二甲基-3-氯-2,5-二氧代咪唑烷-1-基)丙基]吡啶-1-氯化物(ⅩⅢd)和1-正十二烷基-4-[3-(4,4-二甲基-3-氯-2,5-二氧代咪唑烷-1-基)丙氧基]吡啶-1-氯化物(ⅩⅤe)分别达到了同系物中最优的抗菌活性,活性氯浓度0.056 mmol/L时,在5 min内,ⅩⅢd和ⅩⅤe对金黄色葡萄球菌的lg值减少量分别为1.14±0.05和2.74±0.45,对大肠杆菌的lg值减少量分别为0.13±0.01、0.53±0.01。氯胺结构与长链烷基吡啶盐结构具有“协同抗菌”效应。O-alkylated long-chain alkyl pyridinium N-chloramines and n-alkylated long-chain alkyl pyridinium N-chloramines were prepared by multi-step synthesis using 4-hydroxypyridine as linking unit.The structure of precursors and corresponding N-chloramines was confirmed by NMR and HRMS,and the antibacterial activity against Escherichia coli and Staphylococcus aureus of synthetic N-chloramines was preliminarily evaluated using 1-[3-(4,4-dimethyl-3-chloro-2,5-dioxy-imidazolidin-1-yl)propyl]pyridine-1-onium chloride(Ⅱb)as control.The results showed that the antibacterial activity of para-derivative of pyridinium N-chloramine was superior to that of meta-derivative counterpart,with the antibacterial activity increasing significantly with the increase of alkyl chains(-C_(6)H_(13)、-C_(8)H_(17)、-C_(10)H_(2)1、-C_(12)H_(2)5).The antimicrobial activity of N-alkylated long-chain alkyl pyridinium N-chloramines were better than those of O-alkylated long-chain alkyl pyridinium N-chloramines.Specifically,pyridinium N-chloramines containing—C_(12)H_(25)4-n-dodecanoxy-1-[3-(4,4-dimethyl-3-chloro-2,5-dioxy-imidazolidin-1-yl)propyl]pyridine-1-onium chloride(ⅩⅢd)and 1-n-dodecanoxy-4-[3-(4,4-dimethyl-3-chloro-2,5-dioxy-imidazolidin-1-yl)propoxy]pyridine-1-onium chloride(ⅩⅤe)presented the towering antibacterial efficacy.At the active chlorine concentration of 0.056 mmol/L,within 5min,the lg value reduction ofⅩⅢd andⅩⅤe against Staphylococcus aureus was 1.14±0.05 and 2.74±0.45,while the lg value reduction against Escherichia coli was 0.13±0.01 and 0.53±0.01,respectively.There was"synergistic antibacterial"effect between structure of N-chloramines and long-chain alkyl pyridine salts.

关 键 词：4-羟基吡啶 吡啶盐型氯胺 化学合成 抗菌活性 “协同”抗菌 医药原料 

分 类 号：O626[理学—有机化学] TQ421[理学—化学]