Caryophyllene


Caryophyllene, more formally -β-caryophyllene, is a natural bicyclic sesquiterpene that is a constituent of many essential oils, especially clove oil, the oil from the stems and flowers of Syzygium aromaticum, the essential oil of Cannabis sativa, rosemary, and hops. It is usually found as a mixture with isocaryophyllene and α-humulene, a ring-opened isomer. Caryophyllene is notable for having a cyclobutane ring, as well as a trans-double bond in a 9-membered ring, both rarities in nature.
The first total synthesis of caryophyllene in 1964 by E. J. Corey was considered one of the classic demonstrations of the possibilities of synthetic organic chemistry at the time.
Caryophyllene is one of the chemical compounds that contributes to the aroma of black pepper.

Metabolism and derivatives

14-Hydroxycaryophyllene oxide was isolated from the urine of rabbits treated with -caryophyllene. The X-ray crystal structure of 14-hydroxycaryophyllene has been reported.
The metabolism of caryophyllene progresses through -caryophyllene oxide since the latter compound also afforded 14-hydroxycaryophyllene as a metabolite.
Caryophyllene oxide, in which the alkene group of caryophyllene has become an epoxide, is the component responsible for cannabis identification by drug-sniffing dogs and is also an approved food flavoring.

Natural sources

The approximate quantity of caryophyllene in the essential oil of each source is given in square brackets :
Caryophyllene is a common sesquiterpene among plant species. It is biosynthesized from the common terpene precursors dimethylallyl pyrophosphate and isopentenyl pyrophosphate. 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. This further reacts with a second unit of IPP, also via an SN1-type reaction catalyzed by the enzyme IspA, to form farnesyl pyrophosphate. Finally, FPP undergoes QHS1 enzyme-catalyzed intramolecular cyclization to form caryophyllene.

Compendial status