Formation Of Quinone Methide Intermediate Research Articles

Recent Advances in Quinone Methide Chemistry for Protein-Proximity Capturing

AbstractHere we summarize the most recent findings in the chemical-, photo-, or enzyme-triggered generation of nitrogen and oxygen anions leading to the formation of quinone methide intermediates (QMIs). This short review is divided into two categories: generation of nitrogen and oxygen anions. Based on quinone methide intermediates (QMIs), proximate capture of a wide range of proteins has been widely determined and studied. Generally, the triggers include, photoirradiation using 365/254 nm UV light, small molecules (ROS/TBAF/s-tetrazine), metal catalysis (iridium catalysis), and enzymes (NQO1/β-galactosidase). New directions including far-red light, heat, force, microwave, and more practical approaches are explored and illustrated.1 Introduction2 Generation of the Nitrogen Anion3 Generation of the Oxygen Anion4 Conclusion

ON THE MODELING THE FORMATION OF FLAVONOID OXIDATION DIMERIC PRODUCTS

Dimeric products of the oxidation of flavonoids (including most abundant of them – quercetin) are observed rather often even in the dilute aqueous solutions. For explaining the formation of such products the free-radical and electrochemical oxidation of simpler substrate – 4-isopropyl phenol – is considered. It is shown that the products of these processes correspond with the formation of quinone methide intermediate. The formation of similar intermediates seems to be possible at the oxidation of natural flavonoids. The principal chemical property of quinone methides is conjugated addition of various nucleophylic reagents, including water, as well as the initial phenolic compounds. Just this reaction allows explaining the formation of dimeric oxidation products of both 4-isopropyl phenol and flavonoids.For identification of 4-isopropyl phenol oxidation products the technique of HPLC-MS-MS (mass numbers of most abundant signals of mass spectra) combined with evaluations of hydrophobicity factors and ground state energies of supposed reaction products were used.

Hydroxy-Group-Facilitated Vinylic Iodination of ortho-Vinylnaphthols Using Molecular Iodine

An efficient and simple one-pot method for the iodination of <i>ortho</i>-vinylnaphthols using molecular iodine is disclosed. The reaction is believed to proceed through formation of quinone methide intermediate. The method tolerates different functional groups and provides corresponding <i>ortho</i>-iodovinylnaphthols in good to excellent yields.

ChemInform Abstract: Applications of ortho‐Quinone Methide Intermediates in Catalysis and Asymmetric Synthesis.

AbstractReview: 39 refs.

Applications of ortho-Quinone Methide Intermediates in Catalysis and Asymmetric Synthesis

Ortho-quinone methides are important synthetic intermediates and widely implicated in biological processes. In this Synopsis, recent advances concerning the synthesis and utility of these intermediates are discussed with a particular emphasis on metal-catalyzed formation of quinone methide intermediates. Additionally, applications of these intermediates as partners in asymmetric synthesis will be discussed including methods we have developed that involve the enantioselective Pd-catalyzed formation of ortho-quinone methides and the trapping of aforementioned intermediates with diverse nucleophiles.

Nonlinear Solvent Water Effects in the Excited-State (Formal) Intramolecular Proton Transfer (ESIPT) in m-Hydroxy-1,1-diaryl Alkenes: Efficient Formation of m-Quinone Methides1

The photohydration of hydroxy-substituted 1,1-diaryl alkenes 1−3 has been studied in aqueous CH3CN solution. Evidence for formation of quinone methide intermediates was provided by product studies and by observation of its absorption spectrum by laser flash photolysis. For the meta isomers, the proposed mechanism of m-quinone methide formation probably involves a solvent-mediated (“proton-relay”) excited-state (formal) intramolecular proton transfer (ESIPT) from the phenol hydroxyl group to the β-carbon of the alkene moiety in neutral aqueous CH3CN solution, either in a concerted manner or via two very fast steps. The m-quinone methides are then trapped by water to form the corresponding diaryl ethanol product with high overall quantum yield. Evidence for the ESIPT pathway was provided by fluorescence and LFP measurements. The addition of small amounts of water (<0.8 M in CH3CN) decreased the fluorescence emissions of 1 and 2 with a concomitant increase in production of m-quinone methides. Stern−Volmer an...

Lignin Impact on Fibre Degradation: 2—A Model Study Using Cellulosic Hydrogels

The impact of lignin on cellulose degradation was studied in vitrousing lignocellulosic hydrogels. Hardwood lignin (methoxyl content, 191 mg g−1) was blended with cellulose in homogeneous phase solution (dimethylacetamide/LiCl solvent) in two concentrations (100 and 300 mg g−1) and formed into lignocellulosic beads by dropwise addition of the lignocellulose solutions to an appropriate nonsolvent. The lignin was used before and after hydroxypropylation of the phenolic hydroxyl group. Cellulose degradation from these beads after 24 and 72 h incubation in buffered ruminal fluid was compared to that of control (cellulose) beads and to that of cellulose beads incubated in the presence of lignin. The rate of cellulose degradation from the hydrogels was low (12–16% degradation after 24 h). At 72 h, 21–50% of the cellulose was degraded. Cellulose degradation was enhanced (P<0·01) by lignin blended into the beads, but depressed (P<0·01) by lignin added to the incubation medium. The effect of lignin increased (P<0·001) with lignin concentration. Hydroxypropylation of lignin, which blocks the formation of quinone methide intermediates, enhanced (P<0·001) the increase in cellulose degradation with lignin blending, and reduced (P<0·001) the inhibitory effect of lignin included in the incubation medium.

Lignin Impact on Fibre Degradation: 1—Quinone Methide Intermediates Formedfrom Lignin During In Vitro Fermentation ofCorn Stover*

Experiments were conducted to determine whether formation of quinone methide intermediates from lignin occurs during ruminal fermentation of corn stover, as indicated by nucleophilic addition reaction with sulphur-containing reducing agents. Corn stover leaf and stem fractions harvested at full maturity were incubated in buffered ruminal fluid without reducing agents or with (NH 4 ) 2 SO 4 (S-control), Na 2 S.9H 2 O, cysteine-HCl (cysHCl), or cysHCl plus Na 2 S.9H 2 O ; and in only buffer with or without cysHCl plus Na 2 S.9H 2 O. Mixed reducing agents (cysHCl plus Na 2 S.9H 2 O) enhanced (P < 0.001) in vitro fibre degradation after 48 h, tended to increase solubilisation of fibre (P = 0.07) and dry matter (P = 0.06) in buffer alone, and elevated (P < 0.001) S-content of residual fibre. In vitro incorporation of S into the undegraded fibre was determined for corn stover fractions of varying lignin compositions that were harvested at two maturities (early dent and full maturity) in 2 years. Extent of fibre degradation was correlated with extent of S-incorporation (r=-0.54, P < 0.001), and with lignin methoxyl content (r=-0.84, P < 0.001). The negative association of lignin methoxyl content with digestibility is explained by the relative likelihood of quinone methide intermediate formation from guaiacyl and syringyl units in lignin.

Quinone methide formation from para isomers of methylphenol (cresol), ethylphenol, and isopropylphenol: relationship to toxicity.

The oxidative metabolism and toxicity of the para isomers of methylphenol (cresol), ethylphenol, and isopropylphenol were studied using male Sprague-Dawley rat liver microsomes and precision-cut liver slices. Reactive intermediates from each compound were trapped using radiolabeled glutathione and were detected and quantified by HPLC. Conjugates were collected and their structures determined by fast atom bombardment mass spectrometry and proton nuclear magnetic resonance. During microsomal incubations each test compound formed monoglutathione conjugates with structures which are consistent with the formation of quinone methide intermediates. In each case the glutathione moiety was attached to the benzylic carbon on the alkyl side chain of the phenol. With ethylphenol, which has a prochiral benzylic carbon, two isomeric conjugates were detected. The rate of formation of the glutathione conjugates in liver slice incubations was 4-isopropylphenol > 4-ethylphenol > 4-methylphenol. This correlated with the toxicity of the three compounds in liver slices. At equimolar concentrations 4-isopropylphenol was the most toxic while 4-methylphenol was the least toxic. Depletion of intracellular glutathione was observed in the presence of each test compound which preceded cell death. Enhancement of cellular thiol levels with N-acetylcysteine protected cells from the toxic effects of all three compounds as did inhibition of cytochrome P450 activity with metyrapone. These results suggest the formation of quinone methide intermediates from three alkylphenols during oxidative metabolism and demonstrate a correlation between the amount of reactive intermediate formed and toxicity observed in liver slices.

Spectral evidence for the formation of quinone methide intermediates from 5- and 7-hydroxyflavonoids

The u.v. spectra of 5-and 7-hydroxyflavan-4-ols in acid solution are interpreted in terms of the π-π* transition of quinone methide intermediates; the enhanced reactivity of 4-substituted 7-hydroxyflavans compared to 4-substituted 7-methoxyflavans supports this mechanism which may be operative in the biozynthesis of polyflavonoids (e.g. condensed tannins).

Some photochemical and oxidative conversions of pterocarpans and isoflavans: functional requirements for cyclization of isoflavans to pterocarpans

Photolysis of pterocarpans in methanol or acetic acid provides the first general and also direct method of access to 4-functionalized 2′-hydroxy-3,4-trans-isoflavans by C-ring fission and solvolysis. Spontaneous recyclization to the pterocarpan is governed by functional-dependent factors such as the effective delocalization of the transient 4-carbocation and formation of quinone-methide intermediates. In isolated instances there is also photoreduction to isoflavans, or formation of an 8-hydroxy-9-methoxymethoxypterocarpan by solvolysis following fission of the 8,9-methylenedioxy-ring system. Oxidative conversions of 2′,7-dihydroxyisoflavans to pterocarpans with 2,3-dichloro-5,6-dicyanobenzoquinone in methanol may proceed via unstable quinone methides, or via 4-carbocation intermediates after hydride abstraction. However, appropriate 2′-hydroxy-4′-methoxy-disubstitution provides the first example of selective aromatic methoxylation of the B-ring under oxidative conditions.