ja9612763_si_001.pdf (341.9 kB)
Naphthalene, Phenanthrene, and Pyrene as DNA Base Analogues: Synthesis, Structure, and Fluorescence in DNA
journal contribution
posted on 1996-08-21, 00:00 authored by Rex X.-F. Ren, Narayan C. Chaudhuri, Pamela L. Paris, Rumney, Eric T. KoolWe 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 1α-chlorodeoxyribose precursor. The principal products of
this coupling are the α-anomers of the
deoxyribosides. An efficient method has also been developed for
epimerization of the α-anomers to β-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 1H NOE
experiments
and is also correlated with a single-crystal X-ray structure of one
α-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 α- and β-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 π-stacking in DNA.
In addition, the fluorescence of the phenanthrene and pyrene
nucleosides may make them especially useful as structural
probes.