Synthesis of nucleosides and oligonucleotides containing adducts of acrolein and vinyl chloride

Vinyl chloride and acrolein are important industrial chemicals. Both form D NA adducts, vinyl chloride after enzymatic oxidation to chlorooxirane and a crolein by direct reaction. Reaction at the N-2 position of guanine is a ma jor pathway. The resulting 8-oxoethyl and 3-oxopropyl adducts cyclize spont aneously to hydroxyethano and hydroxypropano derivatives, respectively. The two cyclic adducts have been detected in DNA exposed to these mutagens. A new method has been developed for the synthesis of deoxyguanosine adducts o f chlorooxirane and acrolein, as well as oligonucleotides containing these adducts. Reaction of O-6-[(trimethylsilyl)ethyl]-2-fluoro-2'-deoxyinosine w ith the appropriate aminodiol followed by oxidative cleavage of the diol wi th NaIO4 gave the adducts in excellent yields. Reaction of oligonucleotides containing the halonucleoside with the aminodiols followed by NaIO4 effici ently created the nucleosides in the oligonucleotides. Deoxyadenosine adduc ts were created similarly using 6-chloropurine 9-(2'-deoxyriboside).