Identification of Adducts Formed in the Reaction of the Bacterial Mutagen 3-Chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone with Cytidine

摘要

3-Chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone(CMCF),a strong bacterial mutagen reacts with cytidine in buffered aqueous solutions.The reaction products were separated by preparative HPLC C18 column chromatography and were structurally characterized by UV absorbance,H NMR and C NMR spectroscopy,and mass spectrometry.The main products were identified as 7-(beta-D-ribofuranosyl)-4-carboxy-6-oxo-6,7-dihydro-4H-pyrimido[1,6-a]pyrimidine-3-carbaldehyde(cM_1FA-Cyd),and 7-(beta-D-ribofuranosyl)-6-oxo-6,7-dihydro-4H-pyrimido[1,6-a]pyrimidine-3-carbal-dehyde(M_1FA-Cyd).The highest yields of cM_1FA-Cyd and M_1FA-Cyd,being 12 and 1 mol % respectively,were obtained in the reaction performed at pH 4.6 and 37°C for 7 days.M_1FA-Cyd and cM_1FA-Cyd are structurally related to pfA-dR,the adduct previously identified in the reaction of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-fura-none(MX)or 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone(CMCF)with 2'-deoxyadenosine.