Caryophyllene (), more formally (−)-β-caryophyllene ( BCP), is a natural bicyclic sesquiterpene that occurs widely in nature. Caryophyllene is notable for having a cyclobutane ring, as well as a trans-double bond in a 9-membered ring, both rarities in nature.
Production
Caryophyllene can be produced synthetically,
but it is invariably obtained from natural sources because it is widespread. It is a constituent of many
, especially clove oil, the oil from the stems and flowers of
Syzygium aromaticum (cloves), the essential oil of
Cannabis sativa,
copaiba,
rosemary, and
hops.
[ It is usually found as a mixture with isocaryophyllene (the cis double bond isomer) and humulene (obsolete name: α-caryophyllene), a ring-opened isomer.
]
Caryophyllene is one of the chemical compounds that contributes to the odor of black pepper.
Basic research
β-Caryophyllene is under basic research for its potential action as an agonist of the cannabinoid receptor type 2 (CB2 receptor).
β-Caryophyllene has the highest cannabinoid activity compared to the ring opened isomer α-caryophyllene humulene which may modulate CB2 activity.
Safety
Caryophyllene has been given generally recognized as safe (GRAS) designation by the FDA and is approved by the FDA for use as a food additive, typically for flavoring.
Metabolism and derivatives
14-Hydroxycaryophyllene oxide (Carbon15Hydrogen24Oxygen2) was isolated from the urine of treated with (−)-caryophyllene (C15H24). The X-ray crystal structure of 14-hydroxycaryophyllene (as its acetate derivative) has been reported.[
]
The metabolism of caryophyllene progresses through (−)-caryophyllene oxide (C15H24O) since the latter compound also afforded 14-hydroxycaryophyllene (C15H24O) as a metabolite.
- Caryophyllene (C15H24) → caryophyllene oxide (C15H24O) → 14-hydroxycaryophyllene (C15H24O) → 14-hydroxycaryophyllene oxide (Carbon15Hydrogen24Oxygen2).
Caryophyllene oxide,
Natural sources
The approximate quantity of caryophyllene in the essential oil of each source is given in square brackets ( ):
Biosynthesis
Caryophyllene is a common sesquiterpene among plant species. It is biosynthesized from the common terpene precursors dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP). First, single units of DMAPP and IPP are reacted via an SN1-type reaction with the loss of pyrophosphate, catalyzed by the enzyme GPPS2, to form geranyl pyrophosphate (GPP). This further reacts with a second unit of IPP, also via an SN1-type reaction catalyzed by the enzyme IspA, to form farnesyl pyrophosphate (FPP). Finally, FPP undergoes QHS1 enzyme-catalyzed intramolecular cyclization to form caryophyllene.
Compendial status
Further reading
Notes and references
