Synthesis and Properties of N2,3-Ethenoguanosine and N2,3-Ethenoguanosine 5'-Diphosphate

Article abstract of DOI:10.1021/jo00388a007

N²,3-Ethenoguanosine has not been reported as a product of guanosine reaction with haloacetaldehydes.This is in contrast to the reaction of the ribosides yielding the well-known etheno compounds 1,N⁶-εAdo, 3,N⁴-εCyd, and 1,N²-εGuo.The base, N²,3-ethenoguanine was, however, synthesized, but not by direct reaction.We now report the synthesis of the nucleoside via reaction of O⁶-benzylguanosine with bromoacetaldehyde followed by hydrogenolytic debenzylation in the presence of palladium on charcoal.The structure of N²,3-ethenoguanosine was confirmed by NMR, UV, and FAB-MS data.The conformation of this nucleoside resembles that of guanosine, being predominantly in the anti form.The nucleoside was stable at neutrality, 37 deg C, but depurination was rapid at pH 1,24 deg C, with a t_1/2 = 16 min.In contrast to 1,N²-εGuo, the angular N²,3-etheno derivatives are fluorescent, with the base having considerably higher fluorescence than the nucleoside.N²,3-Ethenoguanosine was converted to the 5'-diphosphate by conventional methods.This compound was a substrate for polynucleotide phosphorylase and could be copolymerized with CDP or ADP.There is little quench of the nucleotide fluorescence in copolymers.The recent report that N²,3-ethenoguanine is detected in chloroacetaldehyde-treated DNA after depurination makes N²,3-etheno modification of the guanine moiety of potential importance in understanding vinyl chloride induced carcinogenesis.