Antineoplastic agents 491. Synthetic conversion of aaptamine to isoaaptamine, 9-demethylaaptamine, and 4-methylaaptamine
Antineoplastic agents 491. Synthetic conversion of aaptamine to isoaaptamine, 9-demethylaaptamine, and 4-methylaaptamine
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DOI：
10.1021/jo0300486
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发表时间：
2004-04-02
影响因子：
3.6
通讯作者：
Knight, JC
中科院分区：
文献类型：
--
作者：
Pettit, GR;Hoffmann, H;Knight, JC
将鱼精蛋白（1）用作合成转化为异鱼精蛋白（2）、9-去甲基鱼精蛋白（5）和4-甲基鱼精蛋白（6）的起始材料。本文报道了一种选择性地使1H-苯并[de][1，6]-萘啶（1）类海绵化合物C-9位O-去甲基化的通用方法。用48%氢溴酸对鱼精蛋白（1）和1-甲基鱼精蛋白（11）进行选择性O-脱甲基化，分别得到9-脱甲基鱼精蛋白（5）和异鱼精蛋白（2）。合成了一系列其他的鱼精蛋白衍生物，并通过X射线方法明确地确定了它们的结构。此外，针对鼠P388淋巴细胞细胞系和人癌细胞系的微型板评价了它们的癌细胞生长抑制特性。还进行了作为PKC信号转导途径抑制剂和针对所选微生物的评价。N-鱼精蛋白衍生物3和5具有广谱抗菌活性。
Aaptamine (1) was used as starting material for synthetic transformation to isoaaptamine (2), 9-demethylaaptamine (5), and 4-methylaaptamine (6). A general method for the selective O-demethylation of such 1H-benzo [de][1,6]-naphthyridine (1) marine sponge constituents at position C-9 has been developed. Selective O-demethylation of aaptamine (1) and 1-methylaaptamine (11) with 48% hydrobromic acid led to 9-demethylaaptamine (5) and isoaaptamine (2), respectively. A selection of other aaptamine derivatives were synthesized, and their structures were unambiguously determined by X-ray methods. In addition, their cancer cell growth inhibitory properties were evaluated against the murine P388 lymphocytic cell line and a minipanel of human cancer cell lines. Evaluation as inhibitors of the PKC signal transduction pathway and against a selection of microorganisms was also undertaken. Aaptamine derivatives 3 and 5 had broad-spectrum antimicrobial activities.