Synthesis and conformation of a dinucleoside monophosphate modified by aniline.
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 N-guanosin-8-ylaniline (rG-An). The latter compound was synthesized by a route that featured nucleophilic displacement by antiline upon an 8-bromoguanosine derivative. A number of attempts to prepare N-(deoxyguanosin-8-yl)aniline (dG-An) by electrophilic 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 stacked states 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 electrophilic reactivity of activated aniline derivatives, may be a cause of this weak biological activity.
Jacobson
M D
MD
Department of Chemistry, New York University, New York 10003.
Shapiro
R
R
Underwood
G R
GR
Broyde
S
S
Verna
L
L
Hingerty
B E
BE
D015226:Dinucleoside Phosphates / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D008968:Molecular Conformation; D015394:Molecular Structure; D013816:Thermodynamics
D015226:Dinucleoside Phosphates; D007202:Indicators and Reagents; C072639:N-(deoxycytidylyl-(3'-5')-guanosin-8-yl)aniline