DESIGN AND SYNTHESIS OF POTENTIAL DNA CROSS-LINKING REAGENTS BASED ON THE ANTHRAMYCIN CLASS OF MINOR GROOVE BINDING-COMPOUNDS
DESIGN AND SYNTHESIS OF POTENTIAL DNA CROSS-LINKING REAGENTS BASED ON THE ANTHRAMYCIN CLASS OF MINOR GROOVE BINDING-COMPOUNDS
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DOI：
10.1021/jo00238a004
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发表时间：
1988-02-05
影响因子：
3.6
通讯作者：
COLE, GM
中科院分区：
文献类型：
--
作者：
CONFALONE, PN;HUIE, EM;COLE, GM
利用计算机分子模拟设计一种潜在的交联剂的G-C丰富的区域的DNA的选择性描述。目标结构亚氨基环氧化物7由N-Boc-脯氨酸甲酯（8）经11步合成。某些关键中间体的氧化还原化学提供了几种令人感兴趣的分子内重排，例如硫代亚胺酯环氧化物22通过过渡物质23-25转化为四环产物26。用铝汞齐还原羟基甲苯磺酸酯21也产生四环化合物，四氢呋喃衍生物30，这是由最初的还原中间体二氢衍生物28衍生的不稳定的亚胺鎓醇29环化的结果。然后，四氢呋喃30的断裂直接产生所需的亚氨基环氧化物7，在单个步骤中产生两种反应性官能团。
The use of computer molecular modeling to design a potential cross-linking reagent selective for the G-C rich regions of DNA is described. The target structure, the imino epoxide 7, is synthesized in 11 steps from N-Boc-proline methyl ester (8). Redox chemistry of certain key intermediates affords several interesting intramolecular rearrangements such as the conversion of the thioimidate epoxide 22 to the tetracylic product 26 via the transient species 23-25. Reduction of the hydroxy tosylate 21 with aluminum amalgam also yields a tetracyclic compound, the tetrahydrofuran derivative 30, a result of the cyclization of the unstable iminium alcohol 29 derived from the initial reduction intermediate, the dihydro derivative 28. A fragmentation of the tetracycle 30 than yields directly the desired imino epoxide 7, generating both reactive functionalities in a single step.