蛇床子素酰胺衍生物的合成及其抗菌活性

Synthesis and antibacterial activities of osthole amide derivatives

蛇床子素经SeO2氧化得到(E)-2-甲基-4-(7-甲氧基-2-氧代-2H-色烯-8-基)-2-丁烯醛(中间体Ⅰ),接着,中间体Ⅰ经NaClO2氧化得到(E)-2-甲基-4-(7-甲氧基-2-氧代-2H-色烯-8-基)-2-丁烯酸(中间体Ⅱ),最后,中间体Ⅱ和不同胺经N,N’-二环己基碳二亚胺(DCC)缩合,制备了15个目标化合物,经1HNMR、13CNMR和MS对目标物进行了确证。体外抗菌活性测试结果表明,该类衍生物呈现潜在的抗菌活性,大多化合物的抗菌活性优于蛇床子素,部分化合物有较优的抗耐甲氧西林金黄色葡萄球菌(MRSA)活性。其中,以(E)-N-(4-三氟甲基苄基)-2-甲基-4-(7-甲氧基-2-氧代-2H-色烯-8-基)-2-丁烯酰胺(Ⅲo)的抗MRSA活性最好,最小抑菌质量浓度为64 mg/L,远优于对照药苯唑西林(256 mg/L)。

(E)-2-Methyl-4-(7-methoxy-2-oxo-2 H-chromen-8-yl)-2-butenal was prepared from osthole by selenium dioxide oxidation(intermediateⅠ). Then, intermediateⅠwas oxidized by sodium chlorite to give(E)-2-methyl-4-(7-methoxy-2-oxo-2 H-chromen-8-yl)-2-butenoic acid(intermediate Ⅱ). Finally, fifteen osthole amide derivatives were prepared by N,N′-dicyclohexylcarbodiimide(DCC) condensation of intermediate Ⅱ with different amines. The compounds were confirmed by 1HNMR, 13CNMR and MS. The test results of antibacterial activity in vitro showed that these derivatives had potential antibacterial activities, most of the target compounds had better antibacterial activity than osthole, and some of them had excellent antibacterial activity against methicillin-resistant staphylococcus aureus(MRSA). Among them,(E)-N-(4-trifluoromethylbenzyl)-2-methyl-4-(7-methoxy-2-oxo-2 H-chromen-8-yl)-2-buteneamide(Ⅲo) had the best anti-MRSA activity with a minimum inhibitory mass concentration of 64 mg/L, which was much better than that of oxacillin(256 mg/L).