5-Cyanoamino-4-imidazolecarboxamide and Nitrosative Guanine Deamination:  Experimental Evidence for Pyrimidine Ring-Opening during Deamination

Abstract

5-Cyanoamino-4-imidazolecarboxamide 4a (R = CH2-O-CH2-CH2-OH) has been synthesized, purified, and fully characterized by MS, MS/MS, HRMS, IR spectroscopy, and by 1H and 13C NMR spectroscopy. It is shown that cyclization of 4a yields the guanine 6a and the isoguanine 12a. Our findings provide experimental evidence in support of our hypothesis that the formation of oxanine and xanthine in nitrosative guanine deamination may proceed via pyrimidine ring-opened intermediates. The observed formation of 6a from the amide 4a (XH2 = NH2) shows that, in analogy, oxanine can be formed from 3 (XH = OH). The formation of 12a from 4a reveals for the first time the possibility that oxanine might be formed by a second pathway that involves electrocyclic reaction of 3. Finally, the new chemistry suggests the possibility for a new dG-to-dG cross-link.

Ammonia elimination from protonated nucleobases and related synthetic substrates

“…Samples were prepared by dissolving 1 mg nucleoside in 1 mL of 1% acetic acid solution. The preparations of the cyanoamine 13 and the thioether 14 have been described previously [21]. The LC-MS studies were performed with a Waters XTerra analytical column (C18, 5 m, 4.5 ϫ 250 mm, Milford, MA) using a solvent gradient (Solvents A and B are 0.1% formic acid and acetonitrile, 1% B at 1 min, 10% B at 3 min, 40% B at 20 min, 1% B at 22 min) at a flow rate of 1.0 mL/min while monitoring at ϭ 254 nm.…”

“…We synthesized cyanoamine 13e (13, ether R ϭ CH 2 OCH 2 CH 2 OH) and studied its cyclization reaction and cross-link formation chemistry [21,22]. The production spectra of [13e ϩ H] ϩ , m/z 226, and [13h ϩ H] ϩ , m/z 152, are reported in Figure 4.…”

“…Moreover, we synthesized 5-cyanoamino-4-imidazolecarboxamide and studied its cyclization chemistry [21] and its proficiency for cross-link formation [22]. The unimolecular dediazoniation of the diazonium ions of adenine and cytosine can proceed without ring-opening but the cations 7 and 11 formed in this way are predicted to undergo facile ring-opening [23,24] to ions 8 and 12, respectively (Scheme 1).…”

Gas‐phase synthesis and detection of the benzenediazonium ion, C6H5N. A joint atmospheric pressure chemical ionization and guided ion beam experiment

“…4 In addition, they represent a suitable model for heteroaromatic diazonium ions implied in DNA base deamination. [5][6][7] The gas-phase chemistry of arenediazonium ions has been experimentally investigated via electrospray ionization of their tetrafluoroborate salts, 8 while quantum chemistry methods have been recently used to study the nucleophilic substitution of nitrogen in the benzenediazonium ion by one water molecule to form protonated phenol. 9 The structure of the benzenediazonium ion is particularly interesting.…”

Synthesis and Structure Activity Relationship of Some Indole Derivatives as Potential Anti-inflammatory Agents

“…[46][47][48] Research in-dicated that α-amino ketones used for the preparation of o-amino-cyanopyrroles were usually obtained in situ [49][50][51] via the reaction of α-hydroxy ketones with amines in acid medium, [52][53][54][55] or via the reaction of α-halo ketones with either amines and/or α-amino acids. 56 As previously mentioned, α-hydroxy ketones and α-halo ketones, malononitriles or suitable substituted alkylidenemalonitrile and primary amines constituted essential components for the synthesis of o-amino-cyanopyrrole derivatives.…”