Stereoselective synthesis of some methyl-substituted steroid hormones and their in vitro cytotoxic activity against human gastric cancer cell line MGC-803
Stereoselective synthesis of some methyl-substituted steroid hormones and their in vitro cytotoxic activity against human gastric cancer cell line MGC-803
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一些甲基取代类固醇激素的立体选择性合成及其对人胃癌细胞株MGC-803的体外细胞毒活性
DOI：
10.1016/j.steroids.2010.05.008
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发表时间：
2010-12-01
期刊：
影响因子：
2.7
通讯作者：
Tang, Jie
中科院分区：
文献类型：
--
作者：
Li, Chun;Qiu, Wenwei;Tang, Jie
通过高立体选择性的1，6-共轭加成反应合成了一系列3-，7-，15-和16-甲基取代的甾体类似物。在CuBr催化下，AlMe(3)与4种甾二烯酮前驱体反应生成相应的C-3和C-7甲基取代甾体的Et同分异构体作为主要产物，其中43的比例达到α/β。没有检测到C-16上的甲基加成的β-同分异构体。但是，在相同的反应条件下，C-15上的不对称甲基加成反应得到主要产物为15个β-同分异构体。初步的合成孔径雷达分析表明，C-7α和C-15β位的甲基取代基对人胃癌细胞株MGC-803的抑制力显著增强。(C)2010 Elsevier Inc.保留所有权利。
A series of 3-, 7-, 15-, and 16-methyl-substituted steroid analogs were synthesized via a highly stereoselective 1,6-conjugate addition. Under the catalysis of CuBr, AlMe(3) reacted with four steroid dienone precursors to afford either the corresponding et-epimer of C-3 and C-7 methyl-substituted steroids as the major products, and the ratio of 43 was up to alpha/beta. No beta-epimer has been detected for methyl addition at C-16. However, under the same reaction conditions, enantioselective methyl addition at C-15 afforded the 15 beta-epimer as the major product. The preliminary SAR analysis showed that the methyl substituents at C-7 alpha and C-15 beta positions lead to a dramatical increase in potency against human gastric cancer cell line MGC-803. (C) 2010 Elsevier Inc. All rights reserved.