Studies on Vitamin B&lt;SUB&gt;1&lt;/SUB&gt; and Related Compounds. CIX. A Novel Cleavage of Thiamin and Its Homologues by the Reaction with Aromatic Aldehydes

Oka, Yoshikazu; Kishimoto, Shinji; Honda, Hiroshi

doi:10.1248/cpb.18.527

Cited by 22 publications

(24 citation statements)

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“…The same products were originally observed by Oka et al. during an attempt to catalyze condensation of benzoin with thiamin promoted by a tertiary amine in ethanol [25]. In that study, it is likely that HBnTh fragmented after it formed.…”

Section: Oka Fragmentation Of 2‐(1‐hydroxybenzyl)‐thiaminsupporting

confidence: 78%

“…The expected ionization of the C2α hydroxyl of HBnTh, followed by formation of benzaldehyde and thiamin, only occurs in more basic solutions and is subject only to specific base catalysis by the solvent lyate ion [26]. The occurrence of fragmentation of HBnTh is readily detected by observing the unique absorbance band at 328 nm that arises from the phenyl thiazole ketone product [25]. The unimolecular rate constant for fragmentation of HBnTh is approximately 10 4 s −1 at 30 °C, which is approximately 100 times larger than the k cat of BFD.…”

Section: Oka Fragmentation Of 2‐(1‐hydroxybenzyl)‐thiaminmentioning

confidence: 99%

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Catalyzing separation of carbon dioxide in thiamin diphosphate‐promoted decarboxylation

Kluger¹,

Rathgeber²

2008

The FEBS Journal

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Decarboxylases and intermediatesThiamin diphosphate (ThDP) is a cofactor that promotes the decarboxylation of 2-ketoacids through formation of covalent derivatives between its C2 thiazolium and the carbonyl of the substrate. Combination of a protein and ThDP in a holoenzyme provides substrate specificity and the general enzymic advantage of reduced translational entropy that favors addition processes [1,2]. The covalent intermediate undergoes cleavage of a bond to a carboxylate group derived from the 2-ketoacid, resulting in production of carbon dioxide. This also produces a residual acyl anion equivalent [3-6] with a delocalized structure that can also be represented as a neutral enamine. The sequence is illustrated for the decarboxylation of pyruvic acid by pyruvate decarboxylases in Scheme 1.Protonation at the basic carbon and elimination of ThDP leads to formation of an aldehyde (giving a net substitution of a proton for carbon dioxide). Oxidation of the same intermediate would yield an acid, while reaction with a carbonyl carbon gives a condensation product. The general route is based on concepts originally developed by Breslow [7][8][9] based on studies of model compounds related to ThDP. Details of reaction patterns within that pathway reveal previously unrecognized aspects of enzymic catalysis [3,10].Synthetic analogs of the covalent intermediates have been prepared and studied in order to arrive at a quantitative understanding of the separate functions of the cofactor and protein [11,12]. Spectroscopic analysis of the conjugates of thiamin and ketoacids has enabled specific and quantitative identification of the coenzyme derivatives bound to proteins in enzymic reactions [13][14][15].

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Section: Oka Fragmentation Of 2‐(1‐hydroxybenzyl)‐thiaminsupporting

confidence: 78%

Section: Oka Fragmentation Of 2‐(1‐hydroxybenzyl)‐thiaminmentioning

confidence: 99%

Catalyzing separation of carbon dioxide in thiamin diphosphate‐promoted decarboxylation

Kluger¹,

Rathgeber²

2008

The FEBS Journal

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“…Unlike the enzymic process, the reactions in solution form additional products upon loss of CO 2 , principally the result of the Oka fragmentation to substituted phenyl thiazole ketones (PTKs) and 2,5-dimethyl-4-amino-1,3-pyrimidine (DMAP) (Figure ). , , …”

Section: Resultsmentioning

confidence: 99%

Charge Dispersion and Its Effects on the Reactivity of Thiamin-Derived Breslow Intermediates

2018

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The enzymic decarboxylation of 2-ketoacids proceeds via their C2-thiazolium adducts of thiamin diphosphate (ThDP). Loss of CO from these adducts leads to reactive species that are known as Breslow intermediates. The protein-bound adducts of the 2-ketoacids and ThDP are several orders of magnitude more reactive than the synthetic analogues in solution. Studies of enzymes are consistent with formulation of protein-bound Breslow intermediates with localized carbanionic character at the reactive C2α position, reflecting the charge-stabilized transition state that leads to this form. Our study reveals that nonenzymic decarboxylation of the related thiamin adducts proceeds to the alternative charge-dispersed enol form of the Breslow intermediate. These differences suggest that the greatly enhanced rate of decarboxylation of the precursors to Breslow intermediates in enzymes arises from maintenance of the carbanionic character at the position from which the carboxyl group departs, avoiding charge dispersion by stabilizing electrostatic interactions with the protein as formulated by Warshel. Applying Guthrie's "no-barrier" addition to Marcus theory also leads to the conclusion that maintaining the tetrahedral carbanion at C2α of the resulting adduct minimizes associated kinetic barriers by avoiding rehybridization as part of steps to and from the intermediate. Finally, maintenance of the reactive energetic carbanion agrees with the concepts of Albery and Knowles as the outcome of evolved enzymic processes.

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“…Those results demonstrate that elimination of bromide is faster than protonation of the Breslow intermediate. In an important contrast, BFDC converts p -(chloromethyl)benzoylformic acid ( p -ClCH 2 BF) to the aldehyde, with only a small amount (0.6%) of the alternative route that releases chloride, indicating that protonation on the enzyme is more rapid than chloride elimination. − …”

mentioning

confidence: 99%

Competing Protonation and Halide Elimination as a Probe of the Character of Thiamin-Derived Reactive Intermediates

2019

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Decarboxylation reactions from comparable thiamin diphosphate- and thiamin-derived adducts of p-(halomethyl)benzoylformic acids in enzymic and non-enzymic reactions, respectively, reveal critical distinctions in otherwise similar Breslow intermediates. The ratio of protonation to chloride elimination from the Breslow intermediate is 102-fold greater in the enzymic process. This is consistent with a lower intrinsic barrier to proton transfer on the enzyme, implicating formation of a localized tetrahedral (sp3) carbanion that is formed as CO2 is produced. In contrast, slower protonation in solution of the decarboxylated intermediate is consistent with formation of a delocalized planar carbanionic enol/enamine. The proposed structural and reactive character of the enzymic Breslow intermediate is consistent with Warshel’s general theory of enzymic catalysis, structural characterization of related intermediates, and the lower kinetic barrier in reactions that occur without changes in hybridization.

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Studies on Vitamin B<SUB>1</SUB> and Related Compounds. CIX. A Novel Cleavage of Thiamin and Its Homologues by the Reaction with Aromatic Aldehydes

Cited by 22 publications

References 0 publications

Catalyzing separation of carbon dioxide in thiamin diphosphate‐promoted decarboxylation

Catalyzing separation of carbon dioxide in thiamin diphosphate‐promoted decarboxylation

Charge Dispersion and Its Effects on the Reactivity of Thiamin-Derived Breslow Intermediates

Competing Protonation and Halide Elimination as a Probe of the Character of Thiamin-Derived Reactive Intermediates

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