Methide Precursors Research Articles

Synthesis of a hairpin pyrrole–imidazole polyamide conjugate containing a quinone methide precursor and vinyl linking group

Standard procedures for elaborating a quinone methide precursor for conjugation to a DNA ligand was not compatible with the presence of a vinyl group. Instead, an acrylate linker was attached by Heck coupling subsequent to o-substitution of the phenolic precursor. This transformation required protection of the phenolic group and use of ethyl acrylate rather than acrylic acid. The presence of the vinyl group also rendered the quinone methide precursor more labile to alkaline conditions than its equivalent saturated derivative and required mild conditions for coupling to the pyrrole–imidazole polyamide.

Generation of o-quinone α-carbomethoxymethide by photolysis of methyl 2-hydroxyphenyldiazoacetate in aqueous solutionDedicated to Professor Dr Z. R. Grabowski and Professor Dr J. Wirz on the occasions of their 75th and 60th birthdays.Electronic supplementary information (ESI) available. Tables S1–S4 of rate data. See http://www.rsc.org/suppdata/cp/b2/b211444p/

Flash photolysis of methyl 2-hydroxyphenyldiazoacetate (8) in dilute aqueous perchloric acid solution and acetic acid and biphosphate ion buffers produced a transient species that was identified as o-quinone α-carbomethoxymethide (9). This structural assignment is based upon solvent isotope effects, the form of buffer catalysis, UV absorption maxima, and the identity of decay rate constants with those determined for the transient obtained by flash photolysis of other, more conventional, quinone methide precursors, namely the benzyl alcohol methyl 2-hydroxy mandelate (10) and its acetate, 2′-acetoxy-2-hydroxyphenylacetate (11).

Biomimetic cycloaddition approach to tropolone natural products via a tropolone ortho-quinone methide.

[reaction: see text] A study toward a possible biomimetic hetero Diels-Alder reaction is reported between humulene and a novel tropolone ortho-quinone methide. A suitable tropolone ortho-quinone methide precursor has been prepared from 3-methyl-2-furoate. Heating the ortho-quinone methide precursor gave a tropolone ortho-quinone methide, which in the presence of humulene underwent a hetero Diels-Alder reaction to give a deoxy analogue of epolone B.

Thermodynamic versus kinetic products of DNA alkylation as modeled by reaction of deoxyadenosine.

Alkylating agents that react through highly electrophilic quinone methide intermediates often express a specificity for the weakly nucleophilic exocyclic amines of deoxyguanosine (dG N(2)) and deoxyadenosine (dA N(6)) in DNA. Investigations now indicate that the most nucleophilic site of dA (N1) preferentially, but reversibly, conjugates to a model ortho-quinone methide. Ultimately, the thermodynamically stable dA N(6) isomer accumulates by trapping the quinone methide that is transiently regenerated from collapse of the dA N1 adduct. Alternative conversions of the dA N1 to the dA N(6) derivative by a Dimroth rearrangement or other intramolecular processes are not competitive under neutral conditions, as demonstrated by studies with [6-(15)N]-dA. Both a model quinone methide precursor and its dA N1 adduct yield a similar profile of deoxynucleoside products when treated with an equimolar mixture of dC, dA, dG, and T. Consequently, the most readily observed products of DNA modification resulting from reversible reactions may reflect thermodynamic rather than kinetic selectivity.

Hydrolytic Stabilization of Protected p-Hydroxybenzyl Halides Designed as Latent Quinone Methide Precursors

The hydrolysis rates of a series of protected p-hydroxybenzyl halides designed to generate a p-quinone methide through 1,6-elimination following photolytic deprotection have been investigated in order to optimize hydrolytic stability. A number of p-hydroxybenzyl halides containing an ether- or carbonate-linked photolabile hydroxy protecting group and a fluoride, chloride, or bromide benzylic leaving group have been synthesized. The hydrolysis rates of these derivatives in different water/acetonitrile mixtures and temperatures have been determined. The hydrolysis half-life of the benzyl bromide with the p-hydroxy protected as the carbonate-linked α-methylnitroveratryl (18c) is more than 750 times that of the ether-linked analogue (16c). These studies afford a Hammett σp+ of +0.28 for the carbonate-linked derivatives compared to a σp+ of −0.39 for the ether-linked derivatives. The theoretical hydrolysis half-life of the most stable benzyl fluoride in 100% water was sufficiently long so as to preclude extrapolation, while the chloride was approximately 50 h, and even the bromide was estimated to be nearly 5 h.

Electron Transfer Reactions in Pulping Systems (VI): Alcohol Bisulfite Pulping

ABSTRACT Compound 1, which incorporates a hex-5-enyl group on a quinone methide precursor, has been used to demonstrate that NaHSO3 in 50% isopropyl alcohol exhibits electron transfer reactions. There is a signifi- cant solvent effect associated with this system since NaHSO3 in aq. NaOH showed very few products typical of an electron transfer system, while 50% isopropyl alcohol by itself at 150°C provided some of the typical products. The electron transfer ability of the 50% isopropyl alcohol/NaHSO3 system increases with increasing temperature but is less than that of aqueous anthrahydroquinone at similar temperatures.

Poly(2,6-dimethyl-1,4-phenylene ether) (PPE) redistribution and its significance in the preparation of PPE/epoxy laminate

To facilitate the PPE /epoxy copolymer formation, PPE was redistributed with phenolic compounds to increase the reactive functional groups per PPE chain. Moreover, the resulting PPE with lower molecular weight improved the resin flow during lamination. An optimized process for producing low molecular weight PPE has been developed. The process was accomplished by redistributing regular PPE (0.46 or 0.40 intrinsic viscosity) with benzoyl peroxide and 4,4′-isopropylidenediphenol (BPA) in toluene. The benzoate group was found to be predominantly incorporated at the PPE chain end and the α carbon of the PPE repeating unit. A portion of the amine-containing phenolic end group, the quinone methide precursor, was oxidized to form a dihydro-1,3-benzoxazine derivative during the redistribution process. However, no dienone structural moiety, a proposed PPE redistribution intermediate, could be identified in the redistributed PPE. Two T g values representing epoxy and PPE phases were usually observed in the PPE /epoxy laminates. Interestingly, the T 8 of the PPE phase was equal to, or higher than, that of the PPE powder from which the laminate was made.

Reactivity of new precursors of quinone methides

The azidomethylene protecting group allows the synthesis of unstable phenolic compounds which are used as quinone methide precursors in the alkylations of alcohols, phenols, azide, thiophenol, amines, enols and enolates.