Autoxidation of a 4-iminoimidazolidin-2-one with a tertiary 5-hydrogen to its 5-hydroxy derivative

Angelova, Violina T.; Vassilev, Nikolay G.; Chauvin, Anne‐Sophie; Koedjikov, Asen H.; Ivanov, Petko M.; Pojarlieff, Ivan G.

doi:10.3998/ark.5550190.0009.b02

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…In DMSO or AcCN, the process was complete upon standing for about a week at room temperature. 10 On the other hand, 1a and 1c were found to be stable under the same conditions. In THF, the batch used was shown to contain peroxides, 1b oxidized readily and completely, more so because of the relatively small substrate concentration of 0.01 M. When the 5-hydroxy compound 1d itself was used as a substrate, practically the same rate constant was observed as that of presumably 1b (Fig.…”

Section: Resultsmentioning

confidence: 88%

Hydrolysis of 4-imino-imidazolidin-2-ones in acid and the mechanism of cyclization of hydantoic acid amides

et al. 2007

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The hydrolysis of iminohydantoins generates the same tetrahedral intermediate as that obtained in the cyclization of hydantoic acid amides to hydantoins. The ratio of the products of imine hydrolysis under kinetic control is determined by the relative height of the barriers of the breakdown of to amide or to hydantoin. Thus the partitioning of products unequivocally proves which is the rate determining step in the cyclization reaction-formation or breakdown of . UV and 1H NMR monitoring of the acid catalyzed hydrolysis of four 5-substituted 4-imino-1-methyl-3-(4-nitrophenyl)imidazolidin-2-ones found hydantoins as the only products. The kinetics of hydrolysis of imines were measured in 0.001-1 M HCl. Contrary to the remaining imines, 1,5-dimethyl-4-imino-3-(4-nitrophenyl)imidazolidin-2-one is readily oxidized as stock solution in THF containing peroxides to 1,5-dimethyl-5-hydroxy-4-imino-3-(4-nitrophenyl)imidazolidin-2-one . In all cases, hydrolysis was found to be zero order with respect to [H+]. As imines are fully protonated under the acidity studied, this is evidence of a transition state of a single positive charge. Comparison of imine hydrolysis rates with previous data on rates of cyclization of the corresponding amides of hydantoic acids allowed conditions (acid concentration, substitution pattern-gem-dimethyl effect) to be found that guaranteed kinetic control of the products obtained. Thus it was unequivocally proven that formation of the tetrahedral intermediate is rate determining in the cyclization of hydantoic acid amides. The small steric effects upon methyl substitution at 5-C and a solvent kinetic isotope effect kH/kD of 1.72 favour a mechanism for imine hydrolysis whereby the rate is limited by water attack on the protonated imine concerted with proton transfer from attacking water to a second water molecule.

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Section: Resultsmentioning

confidence: 88%

Hydrolysis of 4-imino-imidazolidin-2-ones in acid and the mechanism of cyclization of hydantoic acid amides

et al. 2007

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“…Stopped-flow experiments are consistent with our proposal for Fl N5[O] formation, as O 2 oxidized EncM-Fl red into EncM− Fl N5 [O] without detectable formation of a C4a−peroxide or other intermediates (Figure 3B). Moreover, chemical precedence lends further credence for this route, as similar enamine autoxidations 22,23 are proposed to produce protonated superoxide through the net transfer of a hydrogen atom to O 2 22 and N-bound peroxides were previously reported too 24,25 (in the form of more stable N−O−O−t-Bu species). Formation of the anionic SQ may be promoted by hydrogen-bond donors from the protein to stabilize the negative charge in the N1−C2O region.…”

Section: ■ Introductionmentioning

confidence: 69%

Biochemical Establishment and Characterization of EncM’s Flavin-N5-oxide Cofactor

et al. 2015

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The ubiquitous flavin-dependent monooxygenases commonly catalyze oxygenation reactions by means of a transient C4a-peroxyflavin. A recent study, however, suggested an unprecedented flavin-oxygenating species - proposed as the flavin-N5-oxide (FlN5[O]) - as key to an oxidative Favorskii-type rearrangement in the biosynthesis of the bacterial polyketide antibiotic enterocin. This stable superoxidized flavin is covalently tethered to the enzyme EncM and converted into FADH2 (Flred) during substrate turnover. Subsequent reaction of Flred with molecular oxygen restores the postulated FlN5[O] via an unknown pathway. Here we provide direct evidence for the FlN5[O] species via isotope labeling, proteolytic digestion, and high-resolution tandem mass spectrometry of EncM. We propose that formation of this species occurs by hydrogen-transfer from Flred to molecular oxygen, allowing radical coupling of the formed protonated superoxide and anionic flavin semiquinone at N5, before elimination of water affords the FlN5[O] cofactor. Further biochemical and spectroscopic investigations reveal important features of the FlN5[O] species and the EncM catalytic mechanism. We speculate that flavin-N5-oxides may be intermediates or catalytically active species in other flavoproteins that form the anionic semiquinone and promote access of oxygen to N5.

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Chameleonic reactivity of α-amino nitrile-derived ureas. Synthesis of highly functionalized imidazolidin-2-one and imidazolidine-2,4-dione derivatives

et al. 2014

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Autoxidation of a 4-iminoimidazolidin-2-one with a tertiary 5-hydrogen to its 5-hydroxy derivative

Cited by 3 publications

References 12 publications

Hydrolysis of 4-imino-imidazolidin-2-ones in acid and the mechanism of cyclization of hydantoic acid amides

Hydrolysis of 4-imino-imidazolidin-2-ones in acid and the mechanism of cyclization of hydantoic acid amides

Biochemical Establishment and Characterization of EncM’s Flavin-N5-oxide Cofactor

Chameleonic reactivity of α-amino nitrile-derived ureas. Synthesis of highly functionalized imidazolidin-2-one and imidazolidine-2,4-dione derivatives

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