Well folks, it’s time to take a technical dive into the cannabinoids. While this may be somewhat heavy on the chemistry, for those looking for the biochemical background of the hemp/cannabis plant and how it produces all these wonderful molecules, the intellectual rewards will be ample.
We will start with the “mother of all cannabinoids,” CBG.
The biochemical precursors to CBG are hexanoyl CoA, malonyl CoA and geranyldiphosphate. These are the true “mother chemicals” of all cannabinoids. CoA refers to Coenzyme A, an important cofactor for biosynthesis. Those interested in CoA are welcome to search it out, but we will stick to more modest aims here.
3 malonyl CoA and one hexanoyl CoA are stitched together via the enzyme tetraketide synthase to produce a tetraketone intermediate. This reactive molecule is then transformed into olivetolic acid via the action of olivetolic acid cyclase.
The geranyl sidechain is then appended via the aromatic prenyltransferase enzyme by geranyldiphosphate. This then yields cannabigerolic acid, or CBGA.
CBGA is the true precursor for most C5 sidechain cannabinoids. C5 means there is a five-member hydrocarbon chain attached as a tail on the compounds. There are also C3 cannabinoids, which employ another enzyme and cofactor to produce the structural motif with two less carbons in the hydrocarbon sidechain. THCV is an example of a C3 sidechain cannabinoid.
Now back to CBGA. This is an interesting molecule in its own right. Physically, it doesn’t behave “like a cannabinoid” but more like an acidic hydrocarbon. The double bonds in the geranyl sidechain promote “molecule stacking” and the acid moiety, coupled with hydrogen bonding with the phenolic groups, leads to a highly crystalline compound. The flowers produced by plants bred for CBG are full of white crystals of CBGA. Thus, they are much less colored and sticky.
GBGA is a true pain to extract, due to its propensity to crystallize during processing. A fun problem we have solved.
Heating CBGA produces CBG in the classic cannabinoid decarboxylation protocol. CBG is very similar to CBGA in its physical properties: highly crystalline at room temperature. I must say the CBG is one of the more interesting molecules (from a physical chemistry perspective) that I have encountered. Very fluid at temperatures above 35 C, it crystallizes rapidly upon cooling to room temperature.
So that’s CBG in a chemical nutshell. More cannabinoid chemistry to come.