Synthesis and conformation of a dinucleoside monophosphate modified by aniline

Michael D. Jacobson, Robert Shapiro, Graham R. Underwood, Suse Broyde, Lynne Verna, Brian E. Hingerty

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)152-159
Number of pages8
JournalChemical Research in Toxicology
Volume1
Issue number3
StatePublished - 1988

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Dinucleoside Phosphates
Conformations
Derivatives
Substitution reactions
Guanine
Bioactivity
Potential energy
aniline
Carcinogens
Dimers
Amines
Protons
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Molecules

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Jacobson, M. D., Shapiro, R., Underwood, G. R., Broyde, S., Verna, L., & Hingerty, B. E. (1988). Synthesis and conformation of a dinucleoside monophosphate modified by aniline. Chemical Research in Toxicology, 1(3), 152-159.

Synthesis and conformation of a dinucleoside monophosphate modified by aniline. / Jacobson, Michael D.; Shapiro, Robert; Underwood, Graham R.; Broyde, Suse; Verna, Lynne; Hingerty, Brian E.

In: Chemical Research in Toxicology, Vol. 1, No. 3, 1988, p. 152-159.

Research output: Contribution to journalArticle

Jacobson, MD, Shapiro, R, Underwood, GR, Broyde, S, Verna, L & Hingerty, BE 1988, 'Synthesis and conformation of a dinucleoside monophosphate modified by aniline', Chemical Research in Toxicology, vol. 1, no. 3, pp. 152-159.
Jacobson MD, Shapiro R, Underwood GR, Broyde S, Verna L, Hingerty BE. Synthesis and conformation of a dinucleoside monophosphate modified by aniline. Chemical Research in Toxicology. 1988;1(3):152-159.
Jacobson, Michael D. ; Shapiro, Robert ; Underwood, Graham R. ; Broyde, Suse ; Verna, Lynne ; Hingerty, Brian E. / Synthesis and conformation of a dinucleoside monophosphate modified by aniline. In: Chemical Research in Toxicology. 1988 ; Vol. 1, No. 3. pp. 152-159.
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