Dea mi no martefragin A及其衍生物的合成与生物活性(Ⅰ)  

Synthesis and the biological activities of deaminomartefraginA and its derivatives(Ⅰ)

作　　者：缪宇平[1] 闻韧[1] 董肖椿[1] 林志刚[1] 

机构地区：[1]复旦大学药学院合成药物化学教研室,上海200032

出　　处：《中国药物化学杂志》2004年第3期134-139,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金资助项目 (2 9872 0 2 9) ;国际合作项目 (2 0 0 10 14 0 4 17)

摘　　要：目的设计合成deaminomartefraginA及其衍生物并测定其自由基清除、单胺氧化酶抑制和抗肿瘤活性。方法以天然的 2 甲基丁醇为原料制备光学活性的 4 甲基己酸 ;以丙二酸二乙酯为原料制备外消旋的 2 甲基丁酸。再以易得的色氨酸为原料 ,与上述 4 甲基己酸、2 甲基丁酸以及不同取代的苯甲酸分别在DCC催化脱水下缩合得到相应的酰胺 ,通过苄位氧化和分子内环合得到deaminomartefraginA及其侧链不同的衍生物。并对其生物合成前体酰胺进行分离纯化研究。 结果合成了deaminomartefraginA及其衍生物 ,包括其生物合成前体在内共合成 14个新化合物 ,其结构经光谱学测定确证 ,并对目标化合物进行了 3种生物活性的筛选。结论初步的体外生物实验结果表明 :deaminomartefraginA(16 )和化合物 17,18具有较强的自由基清除活性 ,其活性与维生素E相当。化合物 6 ,7,11,12 ,14 ,15具有一定的抗肿瘤活性 ,化合物 14 ,15 ,19有一定的单胺氧化酶抑制活性。Aim To study the synthesis of deaminomartefragin A and its derivatives and then test their free radical scavenging activities,MAO inhibitory activities and antitumor activities.Method (S)-4-methyl-hexanoic acid was prepared from natural(S)-2-methyl-butanol and the (±)-2-methyl-butanoic acid was prepared from malonic ester.The amides were prepared from tryptophan and different acid derivatives by the catalytic dehydration of dicyclohexyl carbodiimide(DCC).Deaminomartefragin A and its derivatives were constructed by the oxidative cyclization of amide using dicholorodicyanoquinone(DDQ).At the same time,the amides as biosynthetic precursors were prepared and studied.Results Deaminomartefragin A and its derivatives were synthesized.There are 14 new compounds synthesized in total including the amides.The structures of these compounds were determined by ~1H-NMR and MS/HRMS.Three kinds of biological activities in vitro were tested for these compounds.Conclusion Deaminomartefragin A(16)and its derivatives 17,18 have free radical scavenging activities almost as strong as that of Vit E.Compounds 6,7,11,12,14,15 possess antitumor activities against a mouse ′s P-388 murine leukemia strain.Compounds 14,15,19 have MAO inhibitory activities.

关 键 词：药物化学 制备 化学合成 deaminomartefragin A 自由基清除 抗肿瘤 MAO抑制剂 

分 类 号：R914[医药卫生—药物化学]