Formation of Six Cyclic 1,N2-Hydroxybromopropanodeoxyguanosine Isomers upon Reaction of 2-Bromoacrolein with 2'-Deoxyguanosine

Article abstract of DOI:10.1021/jo00236a008

As a preliminary study in the investigation of reactions of the genotoxin 2-bromoacrolein (2-BA) with DNA, we treated the aldehyde with 2'-deoxyguanosine (2'-dG).Six isomeric cyclic 1,N²-propano-2'-deoxyguanosine adducts were isolated and characterized by UV, LSIMS, and 1H NMR spectral techniques.The adducts 1a-1d were identified as diastereomeric 3-(2-deoxy-β-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-6-hydroxy-7-bromopyrimido<1,2-a>purin-10(3H)-ones.Adducts 2a and 2b were regioisomeric 7-bromo-8-hydroxy diastereomers.At physiological pH (7.4) and temperature (37 deg C), adducts 1a-1d are hydrolyzed to 6,7-dihydroxypropano-2'-de oxyguanosines.These can be transformed to stable 6,7-dihydroxypropanoguanines by removal of the deoxyribose moiety.The resulting bases can be used as standards for further investigations of reactions of 2-BA with DNA.