Naphthalene, phenanthrene, and pyrene as DNA base analogues: Synthesis, structure, and fluorescence in DNA

被引:217
作者
Ren, RXF [1 ]
Chaudhuri, NC [1 ]
Paris, PL [1 ]
Rumney, S [1 ]
Kool, ET [1 ]
机构
[1] UNIV ROCHESTER,DEPT CHEM,ROCHESTER,NY 14627
关键词
D O I
10.1021/ja9612763
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
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页码:7671 / 7678
页数:8
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