Paper
A General Method for the Synthesis of the N2- and N6- Carcinogenic Amine Adducts of 2‘-Deoxyguanosine and 2‘-Deoxyadenosine1
Published Oct 30, 1999 · F. D. Riccardis, and Radha R. Bonala, F. Johnson
Journal of the American Chemical Society
35
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0
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Abstract
A number of simple arylamino compounds (Figure 1) are well-established as pro-carcinogenic agents. Metabolic activation leads to a series of unstable N-hydroxy derivatives that on solvolysis, give nitrenium ions. The latter, which are regarded as the primary mutagenic/carcinogenic agents attack DNA to give a variety of adducts. Principal among these are the C-8 arylamination products of 2‘-deoxyguanosine (dG) and the N2- and N6-(2-acetylamino)arylation adducts of dG and 2‘-deoxyadenosine (dA), respectively. The latter types of adducts have received little biological attention because synthetic methods for their preparation have been lacking. We now describe a general high-yield method for the synthesis of both of these types of N-arylated 2‘-deoxynucleosides. The key step is a Buchwald−Hartwig coupling reaction between an appropriately protected derivative of dG or dA (1 and 7, respectively) and an o-nitroaryl bromide or triflate (2a−e). Subsequent reduction, acetylation, and deprotection of the N2-adduct...
This study presents a high-yield method for the synthesis of N2- and N6-carcinogenic amine adducts of 2'-deoxyguanosine and 2'-deoxyadenosine, which may serve as potential carcinogenic agents.
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