Quinonemethide compounds

Gunatilaka, A. A. L. Triterpenoid quinonemethide and related compound (celastroloids). In Progress in the Chemistry of Organic Natural Products Hertz, W. Kirby, G. W. Moore, R. E. Steglich, W. Tamm, C., Eds. Springer-Verlag New York, 1996 Vol. 67, 1-123. 

Gross, H. and Keitel, I., a-Substituted phosphonates. 58. A direct phosphorylation of 7,7-bisphosphorylated quinonemethide nucleus with trivalent phosphorus-hydrogen compounds via carbon-carbon cleavage, Phosph., Sulf., Silic. Relat. Elem., 62, 35, 1991. 

One modification that pertains to the present book is the role of anthraquinone (AQ) in the pulping process. Under conditions of alkaline pulping, carbohydrates in the wood reduce AQ into an anion-radical (AQ ). Experiments with lignin quinonemethide as a model compound showed that the AQ anion-radical caused fragmentation of the quinonemethide (Scheme 8.23). 

Dithiazolidines containing o-quinonemethide structural units in the 3,5-positions (e.g. (99)) are converted by reagents with an activated CHj group into a range of condensed heterocyclic compounds not easily accessible otherwise (Scheme 14) <85S535,86PHA283>. 

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... 

Quinones and quinoid compounds (e.g., 1,4-quinone, 1,2-quinone, 1,4-quinonedii-mine, 1,4-quinonemethide) (Figure 14.24) are electrophiles capable of reacting with... 

The same chromophore is present in the p-quinonemethide precursors of DL-pinoresinol (twice) and dehydrodiconiferyl alcohol (once). Measurements in a fast-recording ultraviolet spectrometer (Cary apparatus) indicated a half-life of the quinonemethides of about 1 hour (dilute solution in 70% aqueous dioxane at 20°C. and pH 5.5) (5, 18). They may also become stabilized to a small extent by polymerization (see XLIV). Since the quinonemethide (XXI) has no opportunity to become stabilized by intramolecular prototropy, it adds on external electrolytes, particularly hydroxyl compounds and preferably water 31). 

The observed electrophilic reactivity is indicative of superelectrophilic activation in the dication 173. Other ammonium-carboxonium dications have also been reported in the literature, some of which have been shown to react with benzene or other weak nucleophiles (Table 4).1 42b 57-60 Besides ammonium-carboxonium dications (175-179), a variety of N-heteroaromatic systems (180-185) have been reported. Several of the dicationic species have been directly observed by low-temperature NMR, including 176, 178-180, 183, and 185. Both acidic (175, 180-185) and non-acidic carboxonium (176-177) dicationic systems have been shown to possess superelectrophilic reactivity. The quinonemethide-type dication (178) arises from the important biomolecule adrenaline upon reaction in superacid (entry 4). The failure of dication 178 to react with aromatic compounds (like benzene) suggests only a modest amount of superelectrophilic activation. An interesting study was done with aminobutyric acid... 

Since these dithiocarbamates appeared to be suitable compounds for generating quinonemethide intermediates, we investigated their reaction with sodium sulfide. It was found that 3,5-di-ferf-butyl-4-hydroxybenzyl-2V,N-dimethyldithiocarbamate reacts with sodium sulfide to produce bis (3,5-di-teft-butyl-4-hydroxybenzyl) sulfide, XIII, in essentially quantitative yield (20). 

As mentioned above, treatment of the aldol adducts 150 a/b with NMO produced the phenol 152. The interesting oxidation properties of NMO had previously been investigated by Sulikowski et al. on the model compound 157 [85] (Scheme 40). They observed the formation of the hemiacetal 159 in 60% yield and assumed attack of the nucleophilic N-oxide on the quinonemethide tautomer 158 (or on the anion of 158). A related reaction was observed in our group in which the diol 94 was methoxylated at C-6 to 95 by treatment with methoxide ions [82] (Scheme 27). An internal redox step is postulated to account for the reductive 0-N-bond cleavage with concomitant oxidation of the hydroquinone back to the quinone. Without the presence of perruthenate, aromatization with formation of a C-5 phenolic hydroxy group was observed, a reaction later exploited in the synthesis of angucycline 104-2 [87] (see Scheme 49). Thus, based on similar mechanistic principles, the chemical results of the NMO oxidations were quite different compound 147 gave the C-6 phenol 152 [86] whereas 157/158 were converted to the C-5 phenol 160 [85]. 

Little is known about the overall mechanism of cyclic oligomer formation, although the mechanism of the initial stages of the sequence seems fairly clear. The first chemical event is the reaction of formaldehyde (formed in the Petrolite procedures by depolymerization of paraformaldehyde) with phenol to form 2-hydroxy-methyl- and 2,6-6w(hydroxymethyl)phenols in a base-catalyzed process, as shown in Fig. 3. Such compounds were characterized many years ago50), obtained from the action of aqueous formaldehyde on phenol in basic solution at room temperature. Subsequent condensation between the hydroxymethylphenols and the starting phenol occurs to form linear dimers, trimers, tetramers, etc. via a pathway that might involve o-quinonemethide intermediates which react with phenolate ions in a Michael-like reaction, as portrayed in Fig. 4. The condensation of hydroxymethyl-... 

Eor an early summary of the chloromethylation route , the Claisen rearrangement route and the quinonemethide route see C. D. Gutsche, in Calixarenes A Versatile Class of Macrocyclic Compounds (Eds. J. Vicens and V. Bohmer), Kluwer, Dordrecht, 1990, p. 3. 

The phenolic dibenzodioxocin model produced an isolatable biphenylbiphenol, 36 as well as compound 37, the product of the initial a-0-4 cleavage according to Scheme 16.10. The cleavage of the P-O-4 bond is inhibited by the addition of ethanol to the quinonemethide intermediate. The phenolic moiety forms a quinoneme-thide radical that is thought to form the uncharacterized oligomers. 

A number of celastroloids with extended conjugation has been described [35]. But compounds lacking an insaturation on ring B had not been reported. A compound of this type (74) was also isolated from the roots of M. amazonica by Ch vez et al. [81] as an amorphous white solid, unlike the yellow to red colors exhibited by the rest of the quinonemethide triterpenoids. 

A wide range of biological activities has been described for triterpenes and nor-triterpene quinonemethides. These include anti-inflammatory, anti-hyperlipidemic, antitumour-promotion, hepatoprotective, anti-ulcer, anti-microbial and hypoglycemic activitiy, among others [16,35]. Among the compound mentioned previously in this review, antitumour-promotion, anti-inflammatory, inmunosuppressive, anti-tumour, insecticide and anti-AIDS activities were found and are described below. 

Compounds isolated from Celastraceae had showed cytotoxic activity [3,4]. This property has been related mainly to nor-triterpene quinonemethides, but cytotoxic triterpenes had also been reported [96]. As an example, both, tumor initiation and promotion are inhibited by two triterpenes commonly isolated from the familiy, ursolic and oleanolic acids [16]. 

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