A quinone methide is a type of conjugated

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon- hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

that contain a

cyclohexadiene Cyclohexadiene may refer to: * 1,3-Cyclohexadiene, * 1,4-Cyclohexadiene, See also * Benzene or its theoretical isomer ''1,3,5-Cyclohexatriene'' * Cyclohexene Cyclohexene is a hydrocarbon with the formula C6H10. This cycloalkene is a colorl ...

with a

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containin ...

and an exocyclic

methylidene Methylene (systematically named methylidene and dihydridocarbon; also called carbene) is an organic compound with the chemical formula (also written ). It is a colourless gas that fluoresces in the mid-infrared range, and only persists in dilut ...

or extended alkene unit. It is analogous to a

quinone The quinones are a class of organic compounds that are formally "derived from aromatic compounds benzene.html" ;"title="uch as benzene">uch as benzene or naphthalene] by conversion of an even number of –CH= groups into –C(=O)– groups with ...

, but having one of the

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...

ed oxygens replaced with a carbon. The carbonyl and methylidene are usually oriented either ortho or

para Para, or PARA, may refer to: Businesses and organizations * Paramount Global, traded as PARA on the Nasdaq stock exchange * Para Group, the former name of CT Corp * Para Rubber, now Skellerup, a New Zealand manufacturer * Para USA, formerly ...

to each other. There are some examples of transient synthetic

meta Meta (from the Greek μετά, '' meta'', meaning "after" or "beyond") is a prefix meaning "more comprehensive" or "transcending". In modern nomenclature, ''meta''- can also serve as a prefix meaning self-referential, as a field of study or ende ...

quinone methides.

Properties

Quinone methides are cross-conjugated rather than

aromatic In chemistry, aromaticity is a chemical property of cyclic (ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to sat ...

. Nucleophilic addition at the exo-cyclic double bond will result in rearomatisation, making such reactions highly favourable. As a result, quinone methides are excellent, electrophilic

Michael acceptor In organic chemistry, the Michael reaction or Michael addition is a reaction between a Michael donor (an enolate or other nucleophile) and a Michael acceptor (usually an α,β-unsaturated carbonyl) to produce a Michael adduct by creating a carb ...

s, react quickly with

nucleophiles In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they a ...

and can be easily reduced. They are able to act as

radical scavenger A scavenger in chemistry is a chemical substance added to a mixture in order to remove or de-activate impurities and unwanted reaction products, for example oxygen, to make sure that they will not cause any unfavorable reactions. Their use is wide ...

s via a similar process, a behaviour exploited by certain

polymerisation inhibitor Polymerisation inhibitors (US: polymerization inhibitors) are chemical compounds added to monomers to prevent their auto-polymerisation. Unsaturated monomers such as acrylates, vinyl chloride, butadiene and styrene require inhibitors for both proces ...

s. Quinone methides are more polar than quinones, and therefore more chemically reactive. Simple unhindered quinone methides are short lived

reactive intermediate In chemistry, a reactive intermediate or an intermediate is a short-lived, high-energy, highly reactive molecule. When generated in a chemical reaction, it will quickly convert into a more stable molecule. Only in exceptional cases can these com ...

s 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

cresol Cresols (also hydroxytoluene or cresylic acid) are a group of aromatic organic compounds. They are widely-occurring phenols (sometimes called ''phenolics'') which may be either natural or manufactured. They are also categorized as methylphenols. ...

. Quinone methides can be produced in aqueous solution by photochemical dehydration of o-hydroxybenzyl alcohols (i.e.

salicyl alcohol Salicyl alcohol (saligenin) is an organic compound with the formula C6H4(OH)(CH2OH). It is a white solid that is used as a precursor in organic synthesis. Chemical synthesis Salicyl alcohol can be prepared through the reduction of salicylald ...

Occurrence and applications

Quinones methides are commonly invoked in

biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology ...

, but are rarely observed as long-lived intermediates.

Biosynthesis of dehydroglycine

Quinone methide itself arises by the degradation of

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

, leading ultimately to ''p''-

. Various quinone methides are directly involved in the process of

lignification Lignin is a class of complex organic polymers that form key structural materials in the support tissues of most plants. Lignins are particularly important in the formation of cell walls, especially in wood and bark, because they lend rigidity a ...

(creation of complex

lignin Lignin is a class of complex organic polymers that form key structural materials in the support tissues of most plants. Lignins are particularly important in the formation of cell walls, especially in wood and bark, because they lend rigidity ...

polymers A polymer (; Greek ''poly-'', "many" + '' -mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic an ...

) in plants. Quinone methides have been implicated as the ultimate

cytotoxin Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cell ...

s responsible for the effects of such agents as

antitumor Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality, most commonly as a series of separate treatments (e.g. ...

drugs,

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

, and DNA alkylators. Oxidation to a reactive quinone methide is the mechanistic basis of many phenolic anti-cancer drugs. SclerotizationReaction

Celastrol Celastrol (tripterine) is a chemical compound isolated from the root extracts of '' Tripterygium wilfordii'' (Thunder god vine) and ''Tripterygium regelii'' (Regel's threewingnut). Celastrol is a pentacyclic nortriterpen quinone and belongs to th ...

is a

triterpenoid Triterpenes are a class of chemical compounds composed of three terpene units with the molecular formula C30H48; they may also be thought of as consisting of six isoprene units. Animals, plants and fungi all produce triterpenes, including squale ...

quinone methide isolated from ''

Tripterygium wilfordii ''Tripterygium wilfordii'', or ''léi gōng téng'' (Mandarin) (, Japanese: ''raikōtō''), sometimes called thunder god vine but more properly translated thunder duke vine, is a vine used in traditional Chinese medicine. ''Tripterygium wilfordi ...

'' (Thunder of God vine) and '' Celastrus regelii'' that exhibits

antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricants ...

(15 times the potency of α-tocopherol), anti-inflammatory, anticancer, and insecticidal activities. Pristimerin, the methyl

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...

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 (CatSper).

Taxodone Taxodone is a naturally occurring diterpenoid found in ''Taxodium distichum'' (bald cypress), ''Rosmarinus officinalis'' (rosemary), several salvia species and other plants, along with its oxidized rearrangement product, taxodione. Taxodone and t ...

and its oxidized rearrangement product, taxodione, are

diterpenoid Diterpenes are a class of chemical compounds composed of four isoprene units, often with the molecular formula C20H32. They are biosynthesized by plants, animals and fungi via the HMG-CoA reductase pathway, with geranylgeranyl pyrophosphate being ...

quinone methides found in ''

Taxodium distichum ''Taxodium distichum'' (bald cypress, swamp cypress; french: cyprès chauve; ''cipre'' in Louisiana) is a deciduous conifer in the family Cupressaceae. It is native to the southeastern United States. Hardy and tough, this tree adapts to a wide r ...

'' (bald cypress), ''

Rosmarinus officinalis ''Salvia rosmarinus'' (), commonly known as rosemary, is a shrub with fragrant, evergreen, needle-like leaves and white, pink, purple, or blue flowers, native to the Mediterranean region. Until 2017, it was known by the scientific name ''Rosmar ...

'' (rosemary), several ''

Salvia ''Salvia'' () is the largest genus of plants in the sage family Lamiaceae, with nearly 1000 species of shrubs, herbaceous perennials, and annuals. Within the Lamiaceae, ''Salvia'' is part of the tribe Mentheae within the subfamily Nepetoide ...

'' species and other plants, that display

anticancer An anticarcinogen (also known as a carcinopreventive agent) is a substance that counteracts the effects of a carcinogen or inhibits the development of cancer. Anticarcinogens are different from anticarcinoma agents (also known as anticancer or ant ...

antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cry ...

, insecticide, and antifeedant activities. Maytenoquinone, an isomer of taxodione, is a biologically active quinone methide found in '' Maytenus dispermus''.

Kendomycin Kendomycin is an anticancer macrolide first isolated from ''Streptomyces violaceoruber''. It has potent activity as an endothelin receptor antagonist and anti- osteoporosis agent. It also has strong cytotoxicity against various tumor cell lines. ...

is an

quinone methide

macrolide The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. M ...

first isolated from the bacterium ''

Streptomyces violaceoruber ''Streptomyces violaceoruber'' is a bacterium species from the genus of ''Streptomyces''.Deutsche Sammlung von Mikroorganismen und Zellkulturenbr>/ref> ''Streptomyces violaceoruber'' produces protoactinorhodin, kendomycin, phospholipase A2, g ...

''. It has potent activity as an

endothelin receptor There are at least four known endothelin receptors, ETA, ETB1, ETB2 and ETC, all of which are G protein-coupled receptors whose activation result in elevation of intracellular-free calcium, which constricts the smooth muscles of the blood vessels ...

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 In ancient Roman mythology, Salacia ( , ) was the female divinity of the sea, worshipped as the goddess of salt water who presided over the depths of the ocean. Neptune was her consort. That Salacia was the consort of Neptune is implied by Varr ...

''. Quinone methides tingenone and netzahualcoyonol were isolated from ''

Salacia petenensis ''Salacia petenensis'' is a tropical tree native to Central America. It is found in cloud forests and along the eastern coast of Costa Rica at elevations of 1500 to 1700 m. It flowers from March through May and also in October and November. Th ...

''. Nortriterpenoid quinone methide amazoquinone and (7S, 8S)-7-hydroxy-7,8-dihydro-tingenone were isolated from '' Maytenus amazonica''. An antimicrobial quinone methide, 15 alpha-hydroxypristimerin, was isolated from a South American medicinal plant, '' Maytenus scutioides''.

Quinone dimethides

A quinone dimethide (or "xylylene") is a compound with the formula C₆H₄(=CH₂)₂. Thus they are related to quinone ''mono''methides (the topic of this article) by replacing the keto group with

. A well studied example is tetracyanoquinodimethane.

References

External links

Formation and Stability of Simple Quinone MethidesQuinone methide intermediates in organic PhotochemistryReactive intermediates. Some chemistry of quinone methides
*{{cite journal , doi = 10.1016/S0040-4020(02)00496-9 , volume=58 , title=o-Quinone methides: intermediates underdeveloped and underutilized in organic synthesis , year=2002 , journal=Tetrahedron , pages=5367–5405 , vauthors=Van De Water RW, Pettus TR , issue=27 Functional groups