Reactions with deoxyguanosine of 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone, a model compound for α-hydroxylation of tobacco-specific nitrosamines

Article abstract of DOI:10.1021/ja00266a027

4-(3-Pyridyl)-4-oxobutanediazohydroxide (10) is a likely product of metabolic α-hydroxylation of the tobacco nitrosamines N'-nitrosonornicotine (2) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (1). The reactions of 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone (12), a stable precursor to 10, with deoxyguanosine and H₂O at pH 8 were investigated. Three products of the reaction of 12 with deoxyguanosine were characterized as 2'-deoxy-N-[1-methyl-3-oxo-3-(3-pyridyl)propyl]guanosine (18), 2'-deoxyguanosine 3'-(ethyl carbonate), and 2'-deoxyguanosine 5'-(ethyl carbonate). The adduct 18 was also formed upon reaction of 1-(3-pyridyl)-2-buten-1-one (17) with deoxyguanosine. Whereas the branched chain adduct 18 was the major product formed upon reaction of 12 with deoxyguanosine, the solvolysis of 12 gave mainly the nonrearranged keto alcohol 4-hydroxy-1-(3-pyridyl)-1- butanone (21), with lesser amounts of 3-hydroxy-1-(3-pyridyl)-1-butanone (22) and 17. Possible mechanisms for the formation of 18 are discussed.