Formation of oxalo-substituted etheno derivatives in reactions of mucochloric acid with adenosine, guanosine and cytidine

Mäki, Jukka; Sjöholm, Rainer; Krönberg, Leif

doi:10.1039/a905529k

Cited by 14 publications

(15 citation statements)

References 8 publications

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“…The reaction of guanosine (2) with MCA (1) yielded 10,11 oxalyl ethenoguanosine (3). (20−40%) and ethenoguanosine (4) (a few percent).…”

Section: Resultsmentioning

confidence: 99%

“…8,10,12 The likely course of the reaction giving rise to the products 5 and 6 is depicted in Scheme 3. Even though the predominance of the cyclic form of 1 under the conditions of the experiment is accepted, 8,12,19 the course of the reaction nevertheless must occur through the open-chain form of 1 8,10,12 with which it is in equilibrium. 19 In the open-chain form, it is the aldehyde carbon that is susceptible to attack by a nucleophile and this course is consistent with labeling experiments performed on analogous reactions.…”

Section: Issn 1424-6376mentioning

confidence: 99%

“…The main product formed in the reaction of MCA (1) with guanosine (2) has been identified 10 as oxalyl ethenoguanosine (3); a degradation product of 3, ethenoguanosine (4) was also identified 11 as a minor component of the reaction mixture though potentially it can arise by …”

Section: Introductionmentioning

confidence: 99%

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Regioisomeric α-hydroxy chlorohydrins from the reaction of mucochloric acid and guanosine

Klika¹,

Mäki²,

Sjöholm³

et al. 2006

Arkivoc

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The reaction of mucochloric acid with guanosine produces as the major product oxalyl ethenoguanosine together with a minor amount of its degradation product ethenoguanosine. Also present in trace amounts were two sets of regioisomeric α-hydroxy chlorohydrins consisting of interconverting C-6(7) epimers for both C-7(6) stereoisomers, i.e. a total of four stereoisomers were present for each regioisomeric set. Each regioisomeric set consisted of products where a newly-formed six-membered ring was fused onto the nucleobase, one set via N-1 and N-2 of guanosine, the other via N-2 and N-3. The structural elucidation of the compounds was based on NMR studies ( 1 H, 13 C, and 15 N NMR) and a plausible mechanism for their creation is also presented.

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“…The reaction of guanosine (2) with MCA (1) yielded 10,11 oxalyl ethenoguanosine (3). (20−40%) and ethenoguanosine (4) (a few percent).…”

Section: Resultsmentioning

confidence: 99%

Section: Issn 1424-6376mentioning

confidence: 99%

See 1 more Smart Citation

Regioisomeric α-hydroxy chlorohydrins from the reaction of mucochloric acid and guanosine

Klika¹,

Mäki²,

Sjöholm³

et al. 2006

Arkivoc

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“…Mucochloric acid (MCA, 3,4‐dichloro‐5‐hydroxyfuran‐2(5 H )‐one) and mucobromic acid (MBA, 3,4‐dibromo‐5‐hydroxyfuran‐2(5 H )‐one) are two halohydroxyfuranones that have been shown to be direct genotoxins and potential carcinogens 7–14. DNA adducts of mucohalic acids (MXA) are known, with the isolation of etheno, oxalo etheno, and halopropenal derivatives of guanosine, adenosine, and cytosine 15–22…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9][10][11][12][13][14] DNA adducts of mucohalic acids (MXA) are known, with the isolation of etheno, oxalo etheno, and halopropenal derivatives of guanosine, adenosine, and cytosine. [15][16][17][18][19][20][21][22] In recent years, MXA have also attracted much attention in organic synthesis owing to their high functionalization and availability, and they have been used in the synthesis of heterocycles such as gamma-substituted gamma-butenolides and gamma-lactams, and other furanone derivatives. [23][24][25][26][27][28][29][30][31][32][33][34][35] MXA exist in solution as an equilibrium between two species: [36][37][38][39][40] the cyclic lactone-lactol form ðMXA cl Þ and the openchain aldehyde-acid form ðMXA o op Þ.…”

Section: Introductionmentioning

confidence: 99%

Genotoxic halofuranones in water: isomerization and acidity of mucohalic acids

Gómez‐Bombarelli

González‐Pérez

Pérez‐Prior

et al. 2011

J of Physical Organic Chem

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Among the genotoxic halofuranones formed by chlorination in water are mucochloric acid (MCA, 3,4‐dichloro‐5‐hydroxyfuran‐2(5H)‐one) and mucobromic acid (MBA, 3,4‐dibromo‐5‐hydroxyfuran‐2(5H)‐one). These acids are direct genotoxins and potential carcinogens, with the capacity to alkylate the DNA bases. In recent years, they have also attracted attention in the synthesis of furanone derivatives. Mucohalic acids (MXA) exist in solution as an equilibrium between three species; a cyclic lactone‐lactol , an open‐chain aldehyde‐acid , and the dissociated form of the latter . The distribution of the three species in the equilibrium has synthetic, toxicological, and environmental implications owing to their different functionalization. The case of the neutral open‐chain form is of special interest, since it is expected to be highly reactive. We have experimentally determined the apparent dissociation constant of the cyclic species . Their values suggest that at neutral pH MXA are mostly present as the dissociated carboxylate‐aldehyde. The dissociation constant of the open‐chain neutral species and the cyclization equilibrium constant were determined in water and organic solvents, using density functional theory and ab initio methods. The results suggest that the undissociated aldehyde is a minor species at any given pH. The structure of MXA in solution and the influence of the level of theory on the calculated geometry are discussed. Copyright © 2011 John Wiley & Sons, Ltd.

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Identification of Adducts Formed in the Reactions of Malonaldehyde–glyoxal and Malonaldehyde–methylglyoxal with Adenosine and Calf Thymus DNA

Pluskota-Karwatka

Pawłowicz

Bruszyńska

et al. 2010

Chemistry & Biodiversity

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The reactions of adenosine with malonaldehyde and glyoxal, and with malonaldehyde and methylglyoxal resulted in the formation of one malonaldehyde-glyoxal and one malonaldehyde-methylglyoxal conjugate adduct, respectively. These adducts were isolated and purified by reversed-phase liquid chromatography, and structurally characterized by UV, (1)H- and (13)C-NMR spectroscopy, and mass spectrometry. The malonaldehyde-glyoxal adduct was identified as 8-(diformylmethyl)-3-(beta-D-ribofuranosyl)imidazo[2,1-i]purine (M(1)Gx-A), while the malonaldehyde-methylglyoxal one as 8-(diformylmethyl)-7-methyl-3-(beta-D-ribofuranosyl)imidazo[2,1-i]purine (M(1)MGx-A). Both adducts were also observed in calf thymus DNA when incubated in the respective aldehydes under physiological pH and temperature. Moreover, in the reaction of methylglyoxal and malonaldehyde with adenosine, an additional adduct was formed. This adduct was found to consist of one unit derived from methylglyoxal and one unit from formaldehyde. The adduct was identified as N(6)-(2,3-dihydroxy-2-methylpropanoyl)-9-(beta-D-ribofuranosyl)purine (MGxFA-A). Formaldehyde was found to originate from the commercial methylglyoxal in which it was present as an impurity.

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Formation of oxalo-substituted etheno derivatives in reactions of mucochloric acid with adenosine, guanosine and cytidine

Cited by 14 publications

References 8 publications

Regioisomeric α-hydroxy chlorohydrins from the reaction of mucochloric acid and guanosine

Regioisomeric α-hydroxy chlorohydrins from the reaction of mucochloric acid and guanosine

Genotoxic halofuranones in water: isomerization and acidity of mucohalic acids

Identification of Adducts Formed in the Reactions of Malonaldehyde–glyoxal and Malonaldehyde–methylglyoxal with Adenosine and Calf Thymus DNA

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