Olivetol, also known as 5-pentylresorcinol or 5-pentyl-1,3-benzenediol, is an organic compound found in certain species of

lichen A lichen ( , ) is a composite organism that arises from algae or cyanobacteria living among filaments of multiple fungi species in a mutualistic relationship.precursor Precursor or Precursors may refer to: *Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of unr ...

in various syntheses of

tetrahydrocannabinol Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC'' ...

Occurrence

Olivetol is a naturally occurring organic compound. It is found in certain species of

lichen A lichen ( , ) is a composite organism that arises from algae or cyanobacteria living among filaments of multiple fungi species in a mutualistic relationship.pheromone A pheromone () is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting like hormones outside the body of the secreting individual, to affect the behavio ...

, repellent, or antiseptic. The

cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: ''Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternatively ...

plant internally produces the related substance

olivetolic acid Olivetolic acid is an organic compound that is an intermediate in the biosynthetic pathway of the cannabinoids in ''Cannabis sativa ''Cannabis sativa'' is an annual herbaceous flowering plant indigenous to Eastern Asia, but now of cosmopoli ...

(OLA), which may be involved in the

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

(THC).

Synthesis of THC analogs

Olivetol is used in various methods to produce synthetic analogs of THC. One such method is a

condensation reaction In organic chemistry, a condensation reaction is a type of chemical reaction in which two molecules are combined to form a single molecule, usually with the loss of a small molecule such as water. If water is lost, the reaction is also known as a ...

of olivetol and

pulegone Pulegone is a naturally occurring organic compound obtained from the essential oils of a variety of plants such as ''Nepeta cataria'' (catnip), ''Mentha piperita'', and pennyroyal. It is classified as a monoterpene. Pulegone is a clear colorles ...

. In '' PiHKAL'',

Alexander Shulgin Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American medicinal chemist, biochemist, organic chemist, pharmacologist, psychopharmacologist, and author. He is credited with introducing 3,4-methylenedioxymethamph ...

reports a cruder method of producing the same product by bringing to reaction olivetol and the

essential oil An essential oil is a concentrated hydrophobic liquid containing volatile (easily evaporated at normal temperatures) chemical compounds from plants. Essential oils are also known as volatile oils, ethereal oils, aetheroleum, or simply as the o ...

orange Orange most often refers to: *Orange (fruit), the fruit of the tree species '' Citrus'' × ''sinensis'' ** Orange blossom, its fragrant flower *Orange (colour), from the color of an orange, occurs between red and yellow in the visible spectrum * ...

in the presence of

phosphoryl chloride Phosphoryl chloride (commonly called phosphorus oxychloride) is a colourless liquid with the formula . It hydrolyses in moist air releasing phosphoric acid and fumes of hydrogen chloride. It is manufactured industrially on a large scale from phosp ...

.Shulgin, Alexander T (1991) PiHKAL: 26 A method for the synthesis of THC itself consists of the condensation reaction between olivetol and Δ²-carene oxide.

Legality

The production, possession, and/or distribution of olivetol is not outlawed by any country; however, in the United States, it is a DEA watched precursor.

Biosynthesis

Olivetol is biosynthesized by a

polyketide synthase Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...

(PKS)-type reaction from hexanoyl-CoA and three molecules of

malonyl-CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. Functions It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. Fatty acid biosynthesis Malonyl-CoA provides 2-carbon units to fatty acids and commi ...

by an

aldol condensation An aldol condensation is a condensation reaction in organic chemistry in which two carbonyl moieties (of aldehydes or ketones) react to form a β-hydroxyaldehyde or β-hydroxyketone (an aldol reaction), and this is then followed by dehydration to ...

of a tetraketide intermediate. In 2009, Taura et al. was able to clone a type III PKS named olivetol synthase (OLS) from ''

Cannabis sativa ''Cannabis sativa'' is an annual Herbaceous plant, herbaceous flowering plant indigenous to East Asia, Eastern Asia, but now of cosmopolitan distribution due to widespread cultivation. It has been cultivated throughout recorded history, used as ...

''. This PKS is a

homodimeric In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

protein that consists of a 385 amino acid polypeptide with a molecular mass of 42,585 Da that has high sequence similarity (60-70%) identity to plant PKS's. The data from Taura's study of OLS's enzyme kinetics show that OLS catalyzes a decarboxylative-

to produce olivetol. This is similar to stilbene synthase's (STS) mechanism for converting ''p''-coumaroyl-CoA and malonyl-CoA to

resveratrol Resveratrol (3,5,4′-trihydroxy-''trans''-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Sources ...

. Although olivetol is the decarboxylated form of OLA, it is highly unlikely that OLS produces olivetol from OLA. Crude enzyme extracts prepared from flowers and leaves did not synthesize olivetolic acid, but only yielded olivetol. The exact mechanism of olivetol biosynthesis is as yet unsure, but it is possible that an OLA-forming metabolic complex forms along with OLS. In addition, it also appears that OLS only specifically accepts starter CoA esters with C4 to C8 aliphatic side chains such as hexanoyl-CoA. Final image2

References

{{Use dmy dates, date=April 2017 Tetrahydrocannabinol Alkylresorcinols