含苯丙氨酸结构的异噁唑酰胺衍生物的合成与抗菌活性研究  

Synthesis and antibacterial activities of isoxazolamide derivativescontaining phenylalanine moiety

作　　者：孔晶 李莉玲 卢子聪 杨家强 KONG Jing;LI Li-ling;LU Zi-cong;YANG Jia-qiang(School of Pharmacy,Zunyi Medical University,Zunyi 563000,China;Department of Pharmacy,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,China)

机构地区：[1]遵义医科大学药学院,贵州遵义563000 [2]遵义医科大学附属医院药剂科,贵州遵义563000

出　　处：《化学研究与应用》2023年第7期1680-1685,共6页Chemical Research and Application

基　　金：贵州省卫生健康委科学技术基金项目(gzwkj2021-444)资助;遵义市科技计划项目(遵市科合HZ字[2020]41号)资助。

摘　　要：基于活性结构拼合原理,设计合成系列含苯丙氨酸结构的异噁唑酰胺衍生物进行抗菌活性研究。首先,以Boc-苯丙氨酸为原料,与胺缩合,再脱保护,制得中间体Ⅰ;然后,以取代异噁唑甲酸为原料,与二氯亚砜反应,制得中间体Ⅱ;最后,中间体Ⅰ与Ⅱ缩合,制得目标化合物,经~1H NMR,~(13)C NMR和MS确认结构。采用两倍稀释法测试目标化合物的体外抗菌活性。结果表明,部分衍生物对金葡菌(S.aureus)、大肠杆菌(E.coli)和耐甲氧西林金葡菌(MRSA)有较好的抗菌活性,尤其是化合物Ⅲg的抗菌活性最为显著,对S.aureus、E.coli和MRSA的最小抑菌浓度(MIC)分别为4、16和16μg·mL^(-1),其中,抗E.coli活性与对照药苯唑西林(MIC=16μg·mL^(-1))相当,抗MRSA活性远优于对照药苯唑西林(MIC=256μg·mL^(-1)),值得进一步深入研究。Based on the principle of active group combination,a series of isoxazolamide derivatives containing phenylalanine struc-ture were designed for the study of antibacterial activities.First,the intermediateⅠwas prepared from N-(tert-butoxycarbonyl)-L-phenylalanine by condensation with amine and deprotection.Then,the intermediateⅡwas prepared by reaction of substituted isox-azole carboxylic acid with dichloro sulfoxide.Finally,the target compounds were prepared by condensation of intermediateⅠandⅡ,its structures were confirmed by 1 H NMR,13 C NMR and MS.And the antibacterial activities of the target compounds were tested by the double dilution method.The results showed that some derivatives had good antibacterial activities against S.aureus,E.coli and MRSA,especially compoundⅢg,which had the most significant activities,the MIC for S.aureus,E.coli and MRSA were 4,16 and 16μg·mL^(-1),respectively.And the anti-E.coli activity was equivalent to that of oxacillin,the anti-MRSA activity was far supe-rior to that of oxacillin,which was worth further study.

关 键 词：苯丙氨酸 异噁唑酰胺衍生物 合成 抗菌活性 

分 类 号：O626.2[理学—有机化学]