Quinonemethide formation

Some cleavage takes place even if the phenoHc hydroxyl is blocked as an ether link to another phenylpropane unit and quinonemethide formation is prevented. If the a- or y-carbon hydroxyl is free, alkaH-catalyzed neighboring-group attack can take place with epoxide formation and P-aryloxide elimination. In other reactions, blocked phenoHc units are degraded if an a-carbonyl group is present. 

The cleavage process occurs by p-quinonemethide formation after acetate hydrol-ysis. 

This ester, developed for peptide synthesis, is prepared by the standard DCC coupling protocol and is cleaved reductively with SnCl2 (MeOH, 25°, 5 h) followed by treatment with mild base to effect quinonemethide formation with release of the acid in 75-95% yield. ... 

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

The kinetic product distribution appears to be determined by steric factors ex-substitution favors quinonemethide formation ring substitution favors a,cx-coupling. However, since quinonemethide formation is reversible, the only iso table product is often that from a,a-coupling. 

Hydration has also been recorded by Fischer and Wan , who reported that the phenol derivatives 18, 19 and 20 undergo addition of water to the double bond when they are irradiated in acetonitrile/water. The study has shown that the proposed mechanism of m-quinonemethide (see later for further discussion of quinonemethides) formation probably involves a solvent-mediated proton transfer of the phenolic hydrogen to the -carbon of the alkene moiety. This must occur with the participation of a so-called water trimer. This yields the zwitterion 21 that is responsible for the formation of the products, e.g. 22 from 18. The reactions are efficient with quantum yield values of 0.1-0.24. 

Thus, their ability to reduce the quinone to the "activated" hydroquinone 2 may be enhanced. Indeed, some progress in this direction has been reported. For example, mitomycin C, as well as some 9,10-anthraquinones which are substituted so as to allow quinonemethide formation, have recently been shown to possess significantly enhanced toxicity towards hypoxic tumor cells as compared to analogous oxygen-rich cells. ... 

A large number of anthracycline antibiotics are now known, and the list grows yearly. All of these compounds possess structural features analogous to those of adriamycin and are thus amenable to quinonemethide formation upon bioreduction. Some of the more important members of this series from a biological activity point of view are aklavin, steffimycin, baumycin Ai, A2, Bi, B2, Ci, C29 nogalamycin, musettamycin, rhodirubin A,B, marcellomycin, carminomycin, aclacinomycin A,B, isoquinocycline B, pyrromycin, cinerubin A,B, and rudolphomycin. 

The biosynthesis process, which consists essentially of radical coupling reactions, sometimes followed by the addition of water, of primary, secondary, and phenohc hydroxyl groups to quinonemethide intermediates, leads to the formation of a three-dimensional polymer which lacks the regular and ordered repeating units found in other natural polymers such as cellulose and proteins. 

Chemical Properties. Lignin is subject to oxidation, reduction, discoloration, hydrolysis, and other chemical and enzymatic reactions. Many ate briefly described elsewhere (51). Key to these reactions is the ability of the phenolic hydroxyl groups of lignin to participate in the formation of reactive intermediates, eg, phenoxy radical (4), quinonemethide (5), and phenoxy anion (6) ... 

In the presence of sulfide or sulfhydryl anions, the quinonemethide is attacked and a benzyl thiol formed. The P-aryl ether linkage to the next phenylpropane unit is broken down as a result of neighboring-group attack by the sulfur, eliminating the aryloxy group which becomes reactive phenolate ion (eq. 2). If sulfide is not present, a principal reaction is the formation of the stable aryl enol ether, ArCH=CHOAr. A smaller amount of this product also forms in the presence of sulfhydryl anion. 

Other benzyl radicals, including the parent benzyl radical, give reversible formation of quinonemethide derivatives (typically a mixture of a,p- and cqocoupling products) in competition with a,a-coupling (see also Section... 

An alternative route to phenolate-like EGBs is through the cathodic reduction of quinonemethides, (36), [82, 83]. The advantage of these PBs is that they are reduced at modest potentials, which allow EGB formation to take place in situ, and they are ultimately converted into phenols that are easily reoxidized to (36) either by air or by anodic oxidation (60-70% yield) [82]. The radical anion (36a) is expected to have basicity similar to that of (35) , whereas the pK of the conjugate acid of the dianion formed by further reduction can be assumed close to that of triphenylmethane, 30.6. 

Meanwhile, Freudenberg (17) was the first person who demonstrated the formation of an addition compound from a quinonemethide and sucrose during enzymatic dehydrogenation of coniferyl alcohol in a concentrated sucrose solution. Thereafter, Tanaka (18) observed the formation of a benzyl ester between the quinonemethide of a dilignol and a uronic... 

A stepwise sequence, involving the formation of a quinonemethide, has been proposed.4... 

The most likely lignin condensation reaction during the kraft cook is the formation of diphenylmethane structures 29, 30). These structures are also proposed 14) as being already present in native lignin. Phenolic diphenylmethanes do not exhibit any color, but they can easily be dehydrogenated to quinonemethides 20, 23) or quinonemethide radicals (P). 

Hastbacka 13) proposed the first stage in the reaction between vanillyl alcohol and aqueous sodium hydroxide as the formation of the quinonemethide from vanillyl alcohol. Subsequently, a molecule of quinonemethide reacts with a molecule of vanillyl alcohol forming diguaiacylmethane. 

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