Effective thermal oxidation of isopropanol by an NAD+ model

Lü, Yun; Endicott, Donald; Kuester, William

doi:10.1016/j.tetlet.2007.07.038

Cited by 14 publications

(20 citation statements)

References 18 publications

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“…To our best knowledge, there are no reports in the literature about the kinetics of uncatalyzed reactions between flavins and phenethylamines or suitable model compounds. Thus, an accurate value of the activation barrier in aqueous solution cannot be obtained, although there were several studies performed on other hydride transfer reactions between various substrates and NAD + cofactor, using model systems . The work performed by Hamilton and later by Mariano has shown that flavins react with amines and alcohols in aqueous solution on a timescale of days, but no time‐resolved reaction profile is available.…”

Section: Resultsmentioning

confidence: 99%

Empirical valence bond simulations of the hydride transfer step in the monoamine oxidase B catalyzed metabolism of dopamine

et al. 2014

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Monoamine oxidases (MAOs) A and B are flavoenzymes responsible for the metabolism of biogenic amines such as dopamine, serotonin and noradrenaline. In this work, we present a comprehensive study of the rate-limiting step of dopamine degradation by MAO B, which consists in the hydride transfer from the methylene group of the substrate to the flavin moiety of the FAD prosthetic group. This article builds on our previous quantum chemical study of the same reaction using a cluster model (Vianello et al., Eur J Org Chem 2012; 7057), but now considering the full dimensionality of the hydrated enzyme with extensive configurational sampling. We show that MAO B is specifically tuned to catalyze the hydride transfer step from the substrate to the flavin moiety of the FAD prosthetic group and that it lowers the activation barrier by 12.3 kcal mol⁻¹ compared to the same reaction in aqueous solution, a rate enhancement of more than nine orders of magnitude. Taking into account the deprotonation of the substrate prior to the hydride transfer reaction, the activation barrier in the enzyme is calculated to be 16.1 kcal mol⁻¹, in excellent agreement with the experimental value of 16.5 kcal mol⁻¹. Additionally, we demonstrate that the protonation state of the active site residue Lys296 does not have an influence on the hydride transfer reaction.

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Section: Resultsmentioning

confidence: 99%

Empirical valence bond simulations of the hydride transfer step in the monoamine oxidase B catalyzed metabolism of dopamine

et al. 2014

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“…We have recently reported the kinetic and mechanistic study of the oxidation of 2‐propanol via hydride‐transfer to carbocationic oxidants (R + ) in various solvent systems to form the corresponding ketone product, the hydride reduction products of carbocations (RH) and a proton (Eqn (1), R 1 = R 2 = CH 3 ) 31–33. R + used include PhXn + and 10‐methylacridinium ion.…”

Section: Resultsmentioning

confidence: 99%

Structure–reactivity relationship for alcohol oxidations via hydride transfer to a carbocationic oxidizing agent

Lü¹,

Bradshaw²,

Zhao³

et al. 2011

J of Physical Organic Chem

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Second‐order rate constants were determined for the oxidation of 27 alcohols (R1R2CHOH) by a carbocationic oxidizing agent, 9‐phenylxanthylium ion, in acetontrile at 60 °C. Alcohols include open‐chain alkyl, cycloalkyl, and unsaturated alcohols. Kinetic isotope effects for the reaction of 1‐phenylethanol were determined at three H/D positions of the alcohol (KIEα‐D = 3.9, KIEβ‐D3 = 1.03, KIEOD = 1.10). These KIE results are consistent with those we previously reported for the 2‐propanol reaction, suggesting that these reactions follow a hydride‐proton sequential transfer mechanism that involves a rate‐limiting formation of the α‐hydroxy carbocation intermediate. Structure–reactivity relationship for alcohol oxidations was deeply discussed on the basis of the observed structural effects on the formation of the carbocationic transition state (Cδ+OH). Efficiencies of alcohol oxidations are largely dependent upon the alcohol structures. Steric hindrance effect and ring strain relief effect win over the electronic effect in determining the rates of the oxidations of open‐chain alkyl and cycloalkyl alcohols. Unhindered secondary alkyl alcohols would be selectively oxidized in the presence of primary and hindered secondary alkyl alcohols. Strained C7C11 cycloalkyl alcohols react faster than cyclohexyl alcohol, whereas the strained C5 and C12 alcohols react slower. Aromatic alcohols would be efficiently and selectively oxidized in the presence of aliphatic alcohols of comparable steric requirements. This structure–reactivity relationship for alcohol oxidations via hydride‐transfer mechanism is hoped to provide a useful guidance for the selective oxidation of certain alcohol functional groups in organic synthesis. Copyright © 2011 John Wiley & Sons, Ltd.

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“…Alcohol often behaves as an important reducing agent in the biological system. For example, it is well-known that NAD + is reduced by an alcohol in the presence of dehydrogenase, but only two reports dealing with the reduction of pyridine derivatives by an alcohol in the presence of Brønsted acid are known to the best of our knowledge . Hence, we considered that ethanol served as the hydride source to reduce pyridinium ion 4a that is produced in the reaction of 1a or from 2a by fragmentation.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 4-Substituted 3,5-Dinitro-1,4-dihydropyridines by the Self-Condensation of β-Formyl-β-nitroenamine

et al. 2014

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3,5-Dinitro-1,4-dihydropyridines (DNDHPs) are readily constructed by the acid-promoted self-condensation of β-formyl-β-nitroenamines. In the DNDHPs, one molecule of the nitroenamine serves as a C3N1 building block and the other serves as a C2 block. This synthetic method does not require any special reagents and conditions. When the reaction is conducted in the presence of electron-rich benzene derivatives, arylation at the 4-position of DNDHP is achieved by trapping the 3,5-dinitropyridinium ion intermediate.

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Effective thermal oxidation of isopropanol by an NAD+ model

Cited by 14 publications

References 18 publications

Empirical valence bond simulations of the hydride transfer step in the monoamine oxidase B catalyzed metabolism of dopamine

Empirical valence bond simulations of the hydride transfer step in the monoamine oxidase B catalyzed metabolism of dopamine

Structure–reactivity relationship for alcohol oxidations via hydride transfer to a carbocationic oxidizing agent

Synthesis of 4-Substituted 3,5-Dinitro-1,4-dihydropyridines by the Self-Condensation of β-Formyl-β-nitroenamine

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