Cerium (IV) ammonium nitrate (CAN)-mediated regioselective synthesis and anticancer activity of 6-substituted 5,8-dimethOxy-1,4-naphthoquinone
Cerium (IV) ammonium nitrate (CAN)-mediated regioselective synthesis and anticancer activity of 6-substituted 5,8-dimethOxy-1,4-naphthoquinone
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硝酸铈(IV)铵(CAN)介导的6-取代5,8-二甲氧基-1,4-萘醌的区域选择性合成及其抗癌活性
DOI：
10.1016/j.cclet.2016.10.034
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发表时间：
2017-07-01
影响因子：
9.1
通讯作者：
Li, Shao-Shun
中科院分区：
文献类型：
--
作者：
Huang, Guang;Zhao, Hui-Ran;Li, Shao-Shun
6-在乙酸乙酯/水溶液中，以CAN为催化剂，通过2-取代1，4，5，8-四甲氧基萘的氧化脱甲基反应，以较高的收率选择性地合成了具有良好抗癌前景的取代5，8-O-二甲基-1，4-萘醌（6-DMNQ）。一个有趣的发现是，除了已报道的萘环2位上取代基的吸电子效应之外，6-DMNQ的区域选择性合成在很大程度上依赖于CAN介导的氧化中的空间效应。体外细胞毒性试验显示6-DMNQ对癌细胞和正常细胞具有选择性细胞毒性。此外，大多数含硫6-DMNQ衍生物的抗肿瘤活性优于相应的含氧6-DMNQ衍生物，这为6-DMNQ衍生物的抗肿瘤活性设计提供了一种有效的策略。(C)2016中国化学学会、中国医学科学院药物研究所。Elsevier B. V.出版，保留所有权利。
6-Substituted 5,8-O-dimethyl-1,4-naphthoquinones (6-DMNQ), the promising anticancer scaffolds, were selectively generated by oxidative demethylation of 2-substituted 1,4,5,8-tetramethoxynaphthalenes with CAN in EtOAc/H20 in comparatively high yields. An interesting finding was that apart from the reported electron-withdrawing effects of substituents on position 2 of naphthalene ring, regioselective synthesis of 6-DMNQ was largely dependent on the steric effects in CAN-mediated oxidation. The selective cytotoxicities of 6-DMNQ from the in vitro cell-based assays were exhibited between the cancer cells and normal cells. Moreover, most of sulfur-containing 6-DMNQ derivatives displayed better anticancer activities than the corresponding oxygen-containing ones, which could provide an available strategy for the design of 6-DMNQ derivatives as potential anticancer agents. (C) 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.