Synthesis and conformation of a dinucleoside monophosphate modified by aniline.
Synthesis and conformation of a dinucleoside monophosphate modified by aniline.
复制标题
苯胺修饰的二核苷单磷酸的合成和构象。
DOI：
10.1021/tx00003a005
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发表时间：
1988
影响因子：
4.1
通讯作者：
Hingerty,BE
中科院分区：
文献类型：
--
作者：
Jacobson,MD;Shapiro,R;Underwood,GR;Broyde,S;Verna,L;Hingerty,BE
通过磷酸三酯合成方法，使用dCp和N-鸟苷-8-基苯胺（rG-An）的适当封闭的衍生物，制备了修饰的二核苷单磷酸，N-[脱氧胞苷酰-（3 '-5'）-鸟苷-8-基]苯胺（dCprG-An）。后一种化合物是通过8-溴鸟苷衍生物上的antiline亲核置换路线合成的。用活性苯胺衍生物通过亲电取代制备N-（脱氧鸟苷-8-基）苯胺（dG-An）的许多尝试都失败了。苯胺与8-溴脱氧鸟苷衍生物发生亲核取代反应，只得到N-鸟嘌呤-8-基苯胺。已通过CD、质子磁共振和最小势能计算研究了dCprG-An的构象。显示了具有构象异构体混合物的柔性分子。碱基-碱基堆叠状态占主导地位，相反，含有4-氨基联苯的二聚体结合到鸟嘌呤的8位，其中致癌物-碱基堆叠状态占主导地位。苯胺的致突变和致癌活性远低于许多多环芳香胺。苯胺环的堆积能力减弱，以及活性苯胺衍生物的弱亲电反应性，可能是这种弱生物活性的原因。
The modified dinucleoside monophosphate, N-[deoxycytidylyl-(3'-5')-guanosin-8-yl] aniline (dCprG-An) has been prepared by the phosphotriester synthesis approach, using suitably blocked derivatives of dCp and iV-guanosin-8-ylaniline (rG-An). The latter compound was synthesized by a route that featured nucleophilicdisplacement by antiline upon an 8-bromoguanosine derivative. A number of attempts to prepare iV-(deoxyguanosin-8-yl) aniline (dG-An) by elec-trophilic substitution, using activated aniline derivatives, failed. Nucleophilic substitution reactions of aniline with 8-bromodeoxyguanosine derivatives afforded only the base, N-guanin-8-ylaniline. The conformation of dCprG-An has been studied by CD, proton magnetic resonance, and minimized potential energy calculations. A flexible molecule with a mixture of conformers is indicated. Base-base stackedstates predominate, in contrast to the case of a dimer containing 4-aminobiphenyl bound to the 8-position of guanine, where carcinogen-base stacked states are dominant. The mutagenic and carcinogenic activities of aniline are much less than those of many polycyclic aromatic amines. The diminished stacking ability of the aniline ring, as well as the weak electrophilicreactivity of activated aniline derivatives, may be a cause of this weak biologicalactivity.