α-倒捻子素衍生物合成及其抑制磷酸二酯酶4活性研究  

Synthesis ofα-mangostin derivatives and evaluation of their inhibitory activities towards phosphodiesterase 4

作　　者：邓金辉 黄悦 梁津豪 朱嘉琪 于思[1] 刘昊柏 罗海彬[2] 黄仪有 何细新[1] DENG Jinhui;HUANG Yue;LIANG Jinhao;ZHU Jiaqi;YU Si;LIU Haobai;LUO Haibin;HUANG Yiyou;HE Xixin(School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China)

机构地区：[1]广州中医药大学中药学院,广东广州510006 [2]中山大学药学院,广东广州510006

出　　处：《中山大学学报（自然科学版）（中英文）》2022年第3期53-61,共9页Acta Scientiarum Naturalium Universitatis Sunyatseni

基　　金：国家自然科学基金青年科学基金(82003576);广东省自然资源厅广东省海洋经济发展(海洋六大产业)专项资金(粤自然资合[2020]039)。

摘　　要：以α-倒捻子素为先导化合物设计合成一系列衍生物并测试其对磷酸二酯酶4(PDE4,phosphodiesterase 4)的抑制活性。首先α-倒捻子素在DDQ作用下氧化环合得到中间体1,然后经烷基化、还原、水解、酰化等化学反应合成6-位取代的目标化合物;采用[3H]标记液体闪烁计数法测试了衍生物体外抑制PDE4活性。最终设计、合成了11个目标化合物,其结构经1H NMR、13C NMR、HRMS等波谱数据分析确证。活性测试结果表明7个化合物(4a、4b、5、6、8、11和13)的PDE4抑制活性强于α-倒捻子素,其中化合物5的活性最强(IC_(50)=247 nmol/L)。Derivatives ofα-mangostin were designed and synthesized in this study,and their phospho‐diesterase 4(PDE4)inhibitory activities were evaluated in vitro.The initial substrateα-mangostin was converted into the cyclized compound 1,followed by eleven desired compounds were prepared by alkyla‐tion,hydrolysis,acylation reaction and other methods.The structures of the desired compounds were confirmed by 1H NMR,13C NMR and ESI-(HR)MS.The PDE4 inhibitory activities of these com‐pounds were evaluated in vitro by[3H]liquid scintillation counting method.Among the desired com‐pounds,compounds 4a,4b,5,6,8,11 and 13 showed stronger PDE4 inhibition activity thanα-man‐gostin.Compound 5 exhibited potential PDE4 inhibitory activity with the IC_(50) values of 247 nmol/L.

关 键 词：α-倒捻子素 衍生物 磷酸二酯酶4 抑制剂 

分 类 号：R914.5[医药卫生—药物化学]