Synthesis and characterization of nucleosides and oligonucleotides bearingadducts of butadiene epoxides on adenine N-6 and guanine N-2

Butadiene is a major industrial chemical whose genotoxic effects are attrib uted to the reaction of its oxidized metabolites, butadiene monoepoxide (BD O) and butadiene diepoxide (BDO2), with DNA, Nucleosides and oligonucleotid es containing regio- and stereochemically specific adducts of BDO and the B DO2-related compound, butene 3,4-diol 1,2-epoxide (BDE), on guanine [(2R)- and (2S)-N-2-(1-hydroxy-3-buten-2-yl) and (2R,3R)- and (2S,3S)-N-2-(2,3,4-t rihydroxybutl-yl), respectively] and on adenine [(2R)- and (2S)-N-6-(1-hydr oxy-3-buten-2-yl) and (2R,3R)and (2S,3S)-N-6-(2,3,4-trihydroxybut-1-yl), re spectively] have been prepared by nonbiomimetic routes, For guanine adducts , 2-fluoro-O-6-(trimethylsilylethyl)-2 ' -deox was treated with (2R)- and ( 2S)-2-amino-3-buten-1-ol to give the BDO adducts and with (2R,3R)- and (25, 35)1-amino-2,3,4-butanetriol to produce the BDE adducts; the adducted oligo nucleotides were prepared from 11-mer oligonucleotides containing the halop urine. Adenine adducts were prepared in a similar fashion using 6-chloropur ine 2 ' -deoxyriboside as the reactive purine component.