17-芳基取代去氢表雄酮的合成及其体外抗肿瘤活性研究
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摘要
以去氢表雄酮为起始原料,经乙酰化、酯化、Suzuki反应,水解反应,还原反应得到9种去氢表雄酮衍生物(C-1～C-3,D-1～D-3,E-1～E-3),收率61%～95%,其结构经~1H NMR、~(13)C NMR和ESI-MS表征与确证,利用MTT法研究了所合成的化合物对人前列腺癌细胞DU-145的体外抑制活性,结果表明C-1～C-3和D-1～D-3对DU-145均有一定抑制活性,其中D-1和D-3对DU-145具有较好的抑制活性。
Nine dehydroepiandrosterone derivatives were synthesized using dehydroepiandrosterone as the starting material through a series of reactions including acetylation,esterification,suzuki reaction,hydrolysis and reduction.The yields for the derivatives were in the range between 61% and 95%.The structures were characterized by ~1H NMR,~(13)C NMR and ESI-MS.The in vitro antitumor activities of dehydroepiandrosterone derivatives against human prostate cancer cells(DU-145)were investigated using MTT method.The results showed that D-1,D-3 exhibited well inhibition activities against DU-145.
Nine dehydroepiandrosterone derivatives were synthesized using dehydroepiandrosterone as the starting material through a series of reactions including acetylation,esterification,suzuki reaction,hydrolysis and reduction.The yields for the derivatives were in the range between 61% and 95%.The structures were characterized by ~1H NMR,~(13)C NMR and ESI-MS.The in vitro antitumor activities of dehydroepiandrosterone derivatives against human prostate cancer cells(DU-145)were investigated using MTT method.The results showed that D-1,D-3 exhibited well inhibition activities against DU-145.
引文
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[3]张海明.去氢表雄酮衍生物的合成及抗肿瘤活性研究[D].吉林:延边大学,2018.
[4]崔海伟.表雄酮和去氢表雄酮的并杂环与糖基化修饰及其抗乳腺癌活性研究[D].上海:华东师范大学,2015.
[5]刘佩卉.去氢表雄酮的生物法羟基化修饰研究[D].山东:山东轻工业学院,2010.
[6]陈旺,胡代花,冯自立,等.1α-羟基去氢表雄酮的合成方法改进[J].化学通报,2018,81(10):934-938.
[7]Venkatesh D,Handratta,T,Vasaitis,V,et al.Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens:?Synthesis,in vitro biological activity,pharmacokinetics,and antitumor activity in the LAPC4 human prostate cancer xenograft model[J].Journal of Medicinal Chemistry,2005,48(8):2 972-2 984.
[8]梁光平,杨俊,聂昌平,等.16-卤代苯亚甲基去氢表雄酮的合成及结构表征[J].精细化工中间体,2018,48(1):45-48.
[9]Liu X W,Yao Z,Yang J.1,3-Dipolar cycloaddition enabled isoxazole-fused spiropyrrolidine oxindoles syntheses from 3-methyl-4-nitro-5-alkenyl-isoxazoles and azomethine ylides[J].Tetrahedron,2016,72(10):1 364-1 374.