title: New adducts of chloroethylene oxide and chloroacetaldehyde with pyrimidine nucleosides.
abstract: Pyrimidine nucleosides were treated with chloroethylene oxide (CEO) and 2-chloroacetaldehyde (CAA) in methanol and, following trimethylsilylation, the products were analysed by combined gas chromatography-mass spectrometry (GC-MS). Reaction of CEO with 2'-deoxycytidine gave 3,N4-etheno-2'-deoxycytidine and diadduct isomers in which a 1-hydroxy-2-chloroethyl group was substituted for hydrogen on either deoxyribose hydroxyl group. When the N-3-position of 2'-deoxycytidine was blocked by a methyl group, CEO or CAA added a 2-chlorovinyl group at the exocyclic N4 amino nitrogen, as evidenced by a pair of cis/trans isomers. Reaction of 3-methylcytidine and CEO also gave the cis/trans 2-chlorovinyl base adducts, as well as six isomers with a 1-hydroxy-2-chloroethyl group attached to ribose and nine isomeric diadducts, which are possibly positional and optical isomers. Although CEO and CAA were less reactive towards uracil in 3-methyluridine than to cytosine in 3-methyl(deoxy)-cytidine, both electrophiles were able to alkylate 3-methyluridine on ribose, yielding 1-hydroxy-2-chloroethyl derivatives. These data suggest that CEO and CAA may also yield non-cyclic adducts with cytosine in double-stranded DNA where the N-3 position is of low accessibility. Such adducts are of interest in view of their potential promutagenic properties. The data also imply a new mechanism of reaction of CEO with nucleophiles.
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives*; D055598:Chemical Phenomena; D002621:Chemistry; D003562:Cytidine / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000031:analogs & derivatives; D005027:Ethylene Oxide / Q000031:analogs & derivatives; D008401:Gas Chromatography-Mass Spectrometry; D011741:Pyrimidine Nucleosides; D014529:Uridine / Q000031:analogs & derivatives
chemical_list: D011741:Pyrimidine Nucleosides; D003841:Deoxycytidine; C043208:3-methylcytidine; C008513:3-methyluridine; D003562:Cytidine; C015061:chloroethylene oxide; C004656:chloroacetaldehyde; D000079:Acetaldehyde; D005027:Ethylene Oxide; D014529:Uridine