Quinone methides are cross-conjugated rather than aromatic. Nucleophilic addition at the exo-cyclic double bond will result in rearomatisation, making such reactions highly favourable. As a result quinone methides are excellent Michael acceptors, react quickly with nucleophiles and can be easily reduced. They are able to act as radical scavengers via a similar process, a behaviour exploited by certain polymerisation inhibitors. Quinone methides are more polar than quinones, and therefore more chemically reactive. Simple unhindered quinone methides are short lived reactive intermediates that are not stable enough to be isolated under normal circumstances, they will trimerise in the absence of nucleophiles. Sterically hindered quinone methides can be sufficiently stable to be isolated, with some examples being commercially available.
Preparation
Quinone methides are often prepared by oxidation of the corresponding ortho or para phenoltoluene. Quinone methides can be produced in aqueous solution by photochemical dehydration of o-hydroxybenzyl alcohols .
Occurrence and applications
Quinones methides and their derivatives are common constituents of biological systems. Quinone methanide itself arises by the degradation of tyrosine, leading ultimately to p-cresol. Various quinone methides are directly involved in the process of lignification in plants. Many quinone methides show pronounced biological activity. They have been implicated as the ultimate cytotoxins responsible for the effects of such agents as antitumor drugs, antibiotics, and DNA alkylators. Oxidation to a reactive quinone methide is the mechanistic basis of many phenolic anti-cancer drugs. Celastrol is a triterpenoid quinone methide isolated from Tripterygium wilfordii and Celastrus regelii that exhibits antioxidant, anti-inflammatory, anticancer, and insecticidal activities. Pristimerin, the methyl ester of celasterol, is a triterpenoid quinone methide isolated from Maytenus heterophylla that displays antitumor and antiviral activities. Pristimerin has also been found to have a contraceptive effect due to its inhibiting effect on the calcium channel of sperm. Taxodone and its oxidized rearrangement product, taxodione, are diterpenoid quinone methides found in Taxodium distichum, Rosmarinus officinalis, several Salvia species and other plants, that display anticancer, antibacterial, antioxidant, antifungal, insecticide, and antifeedant activities. Maytenoquinone, an isomer of taxodione, is a biologically active quinone methide found in Maytenus dispermus. Kendomycin is an antitumor antibacterial quinone methide macrolide first isolated from the bacterium Streptomyces violaceoruber. It has potent activity as an endothelin receptor antagonist and anti-osteoporosis agent. Elansolid A3 is a quinone methide from the bacterium Chitinophaga sancti that displays antibiotic activity. Antibacterial quinone methides, 20-epi-isoiguesterinol, 6-oxoisoiguesterin, isoiguesterin and isoiguesterinol were found in Salacia madagascariensis. Quinone methides tingenone and netzahualcoyonol were isolated from Salacia petenensis. Nortriterpenoid quinone methide amazoquinone and -7-hydroxy-7,8-dihydro-tingenone were isolated from Maytenus amazonica. An antimicrobial quinone methide, 15 alpha-hydroxypristimerin, was isolated from a South Americanmedicinal plant, Maytenus scutioides.
Analogues
A quinone dimethide is a related derivative in which the carbonyl group is replaced by another methylene group. A well studied example is tetracyanoquinodimethane.
