肉桂酰胺衍生物的合成与抗菌活性

Synthesis and antibacterial activities of cinnamamide derivatives

为了寻找抗菌候选化合物,在前期研究基础上,对蛇床子素结构进行简化与衍生,在甲醇钠/无水乙醇条件下水解,得到(E)-2-羟基-3-异戊烯基-4-甲氧基肉桂酸(Ⅰ),中间体Ⅰ再与胺缩合制备了17个目标物(Ⅱa~q),经1HNMR、13CNMR和MS对目标物进行了结构确证。体外抗菌活性测试结果表明,结构简化后的衍生物呈现较好的抗菌活性。其中,化合物Ⅱh[(E)-3-(2-羟基-4-甲氧基-3-异戊烯基)苯基-N-(4-氟苄基)丙烯酰胺]和Ⅱp[(E)-3-(2-羟基-4-甲氧基-3-异戊烯基)苯基-N-(4-三氟甲基苄基)丙烯酰胺]的活性最为突出,前者对金黄色葡萄球菌(S.aureus)和耐甲氧西林金黄色葡萄球菌(MRSA)的最小抑菌浓度(MIC)分别为16和32 mg/L,后者对S.aureus和MRSA的MIC分别为8和16 mg/L,两个化合物的抗S.aureus活性与对照药苯唑西林较接近,抗MRSA活性远优于对照药苯唑西林。

In order to obtain compounds with antibacterial activites,intermediate(E)-2-hydroxy-3-isopentenyl-4-methoxy cinnamic acid(Ⅰ)was firstly synthesized from hydrolysis of osthole in sodium methoxide/anhydrous ethanol based on previous studies.Seventeen target compounds(Ⅱa~q)were then designed and synthesized by condensation of intermediateⅠwith different amines,and confirmed by 1HNMR,13CNMR and MS.Data from in vitro antibacterial analysis showed that the derivatives with simplified structure displayed better antibacterial performance,of which compoundsⅡh[(E)-3-(2-hydroxy-4-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-N-(4-fluorobenzyl)acrylamide]andⅡp[(E)-3-(2-hydroxy-4-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-N-(4-trifluoromethylbenzyl)acrylamide]exhibited the most prominent antibacterial activities.The minimum inhibitory concentration(MIC)of the former to Staphylococcus aureus(S.aureus)and methicillin-resistant Staphylococcus aureus(MRSA)were 16 and 32 mg/L,respectively,while that of the latter were 8 and 16 mg/L,respectively.Both the two compounds showed similar anti-S.aureus but enhanced anti-MRSA activity in comparison to control oxacillin.