Naphthalene, phenanthrene, and pyrene as DNA base analogues: Synthesis, structure, and fluorescence in DNA
Naphthalene, phenanthrene, and pyrene as DNA base analogues: Synthesis, structure, and fluorescence in DNA
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DOI：
10.1021/ja9612763
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发表时间：
1996-08-21
影响因子：
15
通讯作者：
Kool, ET
中科院分区：
文献类型：
--
作者：
Ren, RXF;Chaudhuri, NC;Kool, ET
我们描述的合成，结构，和DNA掺入脱氧核糖核苷携带多环芳烃作为DNA的“基地”类似物。新的多环化合物是1-萘基、2-萘基、9-菲基和1-芘基脱氧核苷。使用最近开发的涉及芳香族化合物的有机镉衍生物与1 α-氯脱氧核糖前体偶联的C-糖苷键形成方法合成化合物。这种偶联的主要产物是脱氧核苷的α-端基异构体。还开发了一种有效的方法，通过酸催化平衡将α-端基异构体差向异构化为β-端基异构体;这种异构化在四个多环核苷以及两个取代的苯基核苷上成功地进行。异头取代的几何形状来自H-1 NOE实验，也与一个α-异构体的单晶X-射线结构相关。三个多环C-核苷衍生物通过其亚磷酰胺衍生物掺入DNA寡核苷酸中;芘基和菲基衍生物在DNA序列中显示出荧光。结果（1）拓宽了我们的C-糖苷偶联反应的范围，（2）表明（使用新的酸催化差向异构化）α-和β-端基异构体都很容易合成，（3）构成一类新的脱氧核苷衍生物。这种核苷类似物可用作生物物理探针，用于研究非共价相互作用，如DNA中的芳香族α-堆积。此外，菲和芘核苷的荧光可能使它们特别有用的结构探针。
We describe the synthesis, structures, and DNA incorporation of deoxyribonucleosides carrying polycyclic aromatic hydrocarbons as the DNA ''base'' analogue. The new polycyclic compounds are 1-naphthyl, 2-naphthyl, 9-phenanthrenyl, and 1-pyrenyl deoxynucleosides. The compounds are synthesized using a recently developed C-glycosidic bond formation method involving organocadmium derivatives of the aromatic compounds coupling with a 1 alpha-chlorodeoxyribose precursor. The principal products of this coupling are the alpha-anomers of the deoxyribosides. An efficient method has also been developed for epimerization of the alpha-anomers to beta-anomers by acid-catalyzed equilibration; this isomerization is successfully carried out on the four polycyclic nucleosides as well as two substituted phenyl nucleosides. The geometry of the anomeric substitution is derived from H-1 NOE experiments and is also correlated with a single-crystal X-ray structure of one alpha-isomer. Three of the polycyclic C-nucleoside derivatives are incorporated into DNA oligonucleotides via their phosphoramidite derivatives; the pyrenyl and phenanthrenyl derivatives are shown to be fluorescent in a DNA sequence. The results (1) broaden the scope of our C-glycoside coupling reaction, (2) demonstrate that (using a new acid-catalyzed epimerization) both alpha- and beta-anomers are easily synthesized, and (3) constitute a new class of deoxynucleoside derivatives. Such nucleoside analogues may be useful as biophysical probes for the study of noncovalent interactions such as aromatic alpha-stacking in DNA. In addition, the fluorescence of the phenanthrene and pyrene nucleosides may make them especially useful as structural probes.