4552-61-8Relevant articles and documents
Reaction of arylnitrenium ions with guanine derivatives: N1-methylguanosine and N2,N2-dimethylguanosine
Cheng, Bernice,McClelland, Robert A.
, p. 1881 - 1886 (2007/10/03)
A prior flash photolysis study of the direct reaction of arylnitrenium ions with 2′-deoxyguanosine identified a second intermediate that grew in as the transient nitrenium ion reacted with the nucleoside. This intermediate was identified as the the product of the addition of the nitrenium ion to the C-8 position of guanine prior to loss of the C-8 proton - the C-8 intermediate. A feature of the C-8 intermediate is that it exists in acid-base forms. This behavior was evident in both a spectroscopic analysis as well as in the rate-pH profile, which showed a break around pH 4 from a pH-independent reaction to a reaction that was first-order in H+. The present study was designed to identify the structure of the conjugate base form. This involved a kinetic study of the decay of the C-8 intermediate derived from the reaction of the 2-fluorenylnitrenium ion with N1-methylguanosine and N2,N2-dimethylguanosine. The rationale was that the former is unable to lose the N-1 proton, while the latter cannot deprotonate at the NH2 group. The rate-pH profiles clearly show that it is the N-1 proton that is acidic. The rate constants for the C-8 intermediate of N2,N2-dimethylguanosine show the same downward break observed with 2′-deoxyguanosine and guanosine associated with conversion to the conjugate base form. In contrast, the rate constants for the N1-methylguanosine intermediate are independent of pH. Rate constants for the reaction forming the C-8 intermediate are also reported. These show that the reaction of nitrenium ions with the N2,N2-dimethylguanine derivative is significantly faster (except where the reactions are diffusion controlled). This is consistent with the initial step of the reaction of an arylnitrenium ion and guanine occurring by direct addition at C-8. The developing positive charge in such a reaction can be delocalized to the C-2 position where π donors such as NH2 and NMe2 can exert a stabilizing effect.
O6-(Alkyl/aralkyl)guanosine and 2'-deoxyguanosine derivatives: Synthesis and ability to enhance chloroethylnitrosourea antitumor action
Mounetou, Emmanuelle,Debiton, Eric,Buchdahl, Catherine,Gardette, Daniel,Gramain, Jean-Claude,Maurizis, Jean-Claude,Veyre, Annie,Madelmont, Jean-Claude
, p. 2902 - 2909 (2007/10/03)
A series of O6-(alkyl/aralkyl)guanosines and 2'-deoxyguanosine analogs extended to peracetyl and N2-acetyl derivatives, potentially water soluble, was synthesized. Each was associated with N'-(2-chloroethyl)-N-[2- (methylsulfonyl)eth
Synthesis and Properties of N2,3-Ethenoguanosine and N2,3-Ethenoguanosine 5'-Diphosphate
Kusmierek, Jaroslaw T.,Jensen, David E.,Spengler, Sylvia J.,Stolarski, Ryszard,Singer, B.
, p. 2374 - 2378 (2007/10/02)
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 t1/2 = 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.
