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 in various syntheses of tetrahydrocannabinol.

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, repellent, or antiseptic. The cannabis 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. ...

of tetrahydrocannabinol (THC).

Synthesis of THC analogs

Olivetol is used in various methods to produce synthetic

analogs Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analog ...

of THC. One such method is a condensation reaction of olivetol and pulegone. 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 ...

of orange in the presence of phosphoryl chloride.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 (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 of a tetraketide intermediate. In 2009, Taura et al. was able to clone a type III PKS named

olivetol synthase Olivetol, also known as 5-pentylresorcinol or 5-pentyl-1,3-benzenediol, is an organic compound found in certain species of lichen; it is also a precursor in various syntheses of tetrahydrocannabinol. Occurrence Olivetol is a naturally occurring ...

(OLS) from '' Cannabis sativa''. This PKS is a homodimeric 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- aldol condensation 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