新型肟基取代豆甾类化合物的合成及其抗肿瘤活性  

Synthesis and Antiproliferative Activities of Novel Stigmastane Compounds Substituted with Hydroximino Groups

作　　者：甘春芳[1] 董新[1] 刘晓兰[1] 庞丽萍[1] 庞春玲[1] 黄燕敏[1] 崔建国[1] GAN Chun-fang DONG Xin LIU Xiao-lan PANG Li-ping PANG Chun-ling HUANG Yan-min CUI Jian-guo(College of Chemistry and Material Science, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, Guangxi Teachers Education University, Nanning 530001, China)

机构地区：[1]广西师范学院北部湾环境演变与资源利用教育部重点实验室化学与材料科学学院,广西南宁530001

出　　处：《合成化学》2017年第1期1-8,共8页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21462009;21562007);广西高校科学研究项目(KY2015ZD077)

摘　　要：以豆甾醇为原料,通过臭氧化将豆甾醇的C20—C22键断裂,再经过官能团转换,合成了22-肟基取代的单肟基化合物(3和9),6,22-二肟基取代的双肟基化合物(13和14)及3,6,22-三肟基化合物(17),其中涉及4个中间体(5~8)及目标化合物9,13,14和17共8个新化合物,其结构经~1H NMR,^(13)C NMR,IR和HR-MS(ESI)表征。采用MTT法测试了化合物对人胃癌细胞(SGC-7901)、人肝癌细胞(Bel-7404)和人体乳腺癌细胞株(He La)的体外抗肿瘤活性。结果表明,具有22-肟基取代的3-羟基-5-烯结构的豆甾化合物3对受试细胞均有一定活性,IC50分别为34±2μmol·L^(-1),32±1μmol·L^(-1)和38±3μmol·L^(-1)。但是进一步在甾核上引入肟基或羟基的其他几种类型化合物的抗肿瘤活性没有提高。A series of stigmastane compounds substituted with 22-hydroximino（3,9）,6,22-dihydroximino（13,14） and 3,6,22-trihydroximino（17） were synthesized through ozonation and functional group transformation methods using stigmasterol as starting material.Eight novel compounds including four intermediates（5-8） and target compounds（9,13,14 and 17） were involved.The structures were characterized by^1H NMR,^13C NMR,IR and HR-MS（ESI）.The antiproliferative activities of compounds were evaluated against human gastric carcinoma（SGC-7901）,human cervical carcinoma（HeLa） and human liver carcinoma（Bel-7404） cells.The results showed that compound 3 with 22-hydroximino and 3-hydroxy-5-enekey features displayed distinct antiproliferative activities to these cells with IC50 of 34 ± 2 μmol·L^-1,32 ± 1 μmol·L^-1 and 38 ± 3 μmol·L^-1,respectively,and a further introduction of hydroximino or hydroxyl groupon steroidal nucleus did not enhance the antiproliferative activities of compounds.

关 键 词：豆甾醇 22-肟甾体化合物 合成 抗肿瘤增殖活性 细胞毒性 

分 类 号：O621.3[理学—有机化学] O629.2[理学—化学]