Reactive intermediates. Some chemistry of quinone methides

Abstract

Quinone methides were produced in aqueous solution by photochemical dehydration of o-hydroxybenzyl alcohols (o-HOC 6 H 4 CHROH; R = H, C 6 H 5 , 4-CH 3 OC 6 H 4 ), and flash photolytic techniques were used to examine their rehydration back to starting substrate as well as their interaction with bromide and thiocyanate ions. These reactions are acid-catalyzed and show inverse isotope effects (k H+ /k D+ < 1), indicating that they occur through preequilibrium protonation of the quinone methide on its carbonyl carbon atom followed by rate-determining capture of the benzyl carbocations so formed by H 2 O, Br -, or SCN -. With some quinone methides (R = C 6 H 5 and 4-CH 3 OC 6 H 4 ) this acid catalysis could be saturated, and analysis of the data obtained in the region of saturation for the example with R = 4-CH 3 OC 6 H 4 produced both the equilibrium constant for the substrate protonation step and the rate constant for the rate-determining step. Energy relationships comparing the quinone methides with their benzyl alcohol precursors are derived.

Quinone Methides and their Prodrugs: A Subtle Equilibrium Between Cancer Promotion, Prevention, and Cure

“…14) [99]. These species, although not closely related to standard QMs, as they undergo a [1][2][3][4][5][6][7][8] addition, can be generated in situ by irradiation between 310 and 360 nm. The QMs originating from binaphtols were 100-fold more reactive that the naphthyl QMs, and they were also produced from the water-soluble leaving group, trimethylammonium iodide; the QMs obtained were also able to alkylate DNA.…”

“…QMs exist as two-position isomers: the p-QM (1) and the o-QM (2). Comparing the structures of QM and , -unsaturated ketones leads to three conclusions, as follows:…”

“…This feature may relate to the fact that QMs are closely related to the structure of "simple" , -unsaturated ketones and, in particular, cyclic ones ( Fig. 1) [1,2]. However, if they share some reactive behavior with cyclic ketones, QM drugs and QM-prodrugs also show specific characteristics that render them more interesting for applications in biology [1].…”

Syntheses of chromenes and chromanes via o‐quinone methide intermediates

“…The formation of o ‐QMs as reactive intermediates in biologically active natural products has been reviewed [117, 118]. Apart from their involvement in biological processes, o ‐QMs are also very versatile intermediates in organic synthesis [119–124], but until now they have been less utilized in total syntheses [125]. Since they are ephemeral species [126], they must be generated in situ by processes that involve photolysis of o ‐, m ‐, or p ‐hydroxybenzyl alcohols [127], thermal reactions [128, 129], thermal extrusion of sulfur dioxide [128] and anionic triggered reactions [130, 131].…”

Influence of structural and functional modifications of selected genotoxic carcinogens on metabolism and mutagenicity – a review

“…As a result, it is capable of reacting with both nucleophiles and electrophiles [215]. Quinone-methide is stabilized by the benzene-type resonance of the dipolar form thereby substantially affecting the structure of o-quinone-methide.…”