Synthesis of the fully protected phosphoramidite of the benzene-DNA adduct, N2-(4-hydroxyphenyl)-2'-deoxyguanosine and incorporation of the later into DNA oligomers

N2- (4-Hydroxyphenyl)-2 '-deoxyguanosine-5 '-O-DMT-3 '-phosphoramidite has been synthesized and used to incorporate the N2-(4-hydroxyphenyl)-2 '-dG (N2-4-HOPh-dG) into DNA, using solid-state synthesis technology. The key step to obtaining the xenonucleoside is a palladium (Xantphos-chelated) catalyzed N2-arylation (Buchwald-Hartwig reaction) of a fully protected 2 '-deoxyguanosine derivative by 4-isobutyryloxybromobenzene. The reaction proceeded in good yield and the adduct was converted to the required 5 '-O-DMT-3 '-O-phosphoramidite by standard methods. The latter was used to synthesize oligodeoxynucleotides in which the N2-4-HOPh-dG adduct was incorporated site-specifically. The oligomers were purified by reverse-phase HPLC. Enzymatic hydrolysis and HPLC analysis confirmed the presence of this adduct in the oligomers.