Quinone methides formation

A series of carbamates have been prepared that are cleaved by liberation of a phenol, which, when treated with base, cleaves the carbamate by quinone methide formation through a 1,6-elimination. ... 

Thompson, D. C. Thompson, J. A. Sugumaran, M. Moldeus, P. Biological and toxicological consequences of quinone methide formation. Chem.-Biol. Interact. 1993, 86, 129-162. 

Foster, K. L. Baker, S. Brousmiche, D. W. Wan, P. o-Quinone methide formation from excited state intramolecular proton transfer (ESIPT) in an o-hydroxystyrene. J. Photochem. Photobiol. A Chem. 1999, 129, 157-163. 

SCHEME 7.14 Cyclopropyl quinone methide formation upon reductive activation. The CC-1065 A-ring is shown in the inset. 

SCHEME 7.19 Mechanism for quinone methide formation and fate. 

FIGURE 7.17 pH-rate profile for quinone methide formation. 

Lemus, R. H. Skibo, E. B. Design of pyritnido[4.5-s quinazoline-based anthraquinone mimics, structure-activity relationship for quinone methide formation and the influence of internal hydrogen bonds on quinone methide fate. J. Org. Chem. 1992, 57, 5649-5660. 

Zhou, Q. Zuniga, M. A. Quinone methides formations in the Cu2 + -induced oxidation of a diterpenone catechol and concurrent damage on DNA. Chem. Res. Toxicol. 2005, 18, 382-388. 

SCHEME 9.16 DNA cross-linking by tandem quinone methide formation. 

Bolton, J. L. Thompson, J. A. Oxidation of butylated hydroxytoluene to toxic metabolites factors influencing hydroxylation and quinone methide formation by hepatic and pulmonary microsomes. Drug Melah. Dispos. 1991, 19,467-472. 

Kassahun, K. Pearson, P. G. Tang, W. McIntosh, I. Leung, K. Elmore, C. Dean, D. Wang, R. Doss, G. Baillie, T. A. Studies on the metabolism of troglitazone to reactive intermediates in vitro and in vivo. Evidence for novel biotransformation pathways involving quinone methide formation and thiazolidinedione ring scission. Chem. Res. Toxicol. 2001, 14, 62-70. 

Studies on the metabolism of troglitazone to reactive intermediates in vitro and in vivo. Evidence for novel biotransformation pathways involving quinone methide formation and thiazolidinedione ring scission. Chemical Research in Toxicology, 14 (1), 62—70. 

The double dehydrogenation of o-alkylphenols to chromenes has also been achieved with DDQ, the reaction presumably proceeding through the alkenylphenol rather than the chroman. The latter are not known for their propensity to undergo oxidation by DDQ unless a free hydroxyl group is present to allow quinone methide formation to occur. Once again, substitution at C-3 appears to be essential for success. 

This ester, developed for peptide synthesis, is prepared by the standard DCC coupling protocol, and it is cleaved reductively with SnCl2 (MeOH, 25°C, 5 h) followed by treatment with mild base to effect quinone methide formation with release of the acid in 75-95% yield. Since cleavage is initiated by reduction of the azide group, other reagents that reduce the azide should also cleave this ester. 

Acyloxybenzyl esters were designed to be released under physiological conditions. Porcine liver carboxyesterase efficiently releases the phosphate by acetate hydrolysis and quinone methide formation. In a diester the first ester is cleaved faster than the... 

A quinone methide is a relatively unstable species the unsubstituted case has been reported to have a lifetime of 15 seconds in methanol at room temperature [47], However, more substituted, more hindered quinone methides can be prepared in the presence of water and can have long lifetimes (years) in chloroform solutions [48], The instability of quinone methides can be attributed to facile reactions that regenerate an aromatic system. An anion (nucleophile) can add to the a-carbon to rearomatize the system via a familiar Michael reaction [49], The added anion can also be a leaving group (Figure 10.6, step 1) in other words, quinone methide formation is a reversible reaction... 

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