Concentrates How is THCp Being Made (not looking for a recipe, just a basic outline)?

[purplehaze147]

All the isomers/analogs (∆8;9;10, HHC etc) THC, at least those having a cannabinol (CBN) backbone, can be made fairly easily from CBD or ∆9-THC.

THCp on the other hand has a cannbiphorol backbone, not a cannabinol backbone. I have a chemistry degree (working on getting a bachelor's still though), so I know quite a bit more than the average person about when and how a chemical bond will form. There's no way I can think of to add an extra two carbons to the end of the C5H11 side chain on the aromatic ring. There's no functional groups to work with or anything.

It seems it'd be easier to just do a total synthesis, but instead of using olivetol (5-pentylbenzene-1,3-diol) you'd have to use the 7 carbon chain version of olivetol - 5-heptylbenzene-1,3-diol (I don't know the common name but you can see pentyl is replaced with heptyl). Or can a functional group be added to the end allowing for CBD to still be used? I'm not sure without butchering the molecule up.

 

[purplehaze147]

The 7 carbon chain precursor (for THCp and CBDp) is a lot more rare than the 5 carbon chain precursor (making CBG, CBC, CBD, THC, etc) so there has to be only trace amounts of CBDp too.

Maybe someway to reduce and perform an addition reaction or something. But that seems like goes against the Markovinkov (spelling) rule while not meeting criteria for anti-Markov if it as added to the end on the chain instead of branching. Still it seems like I'd have to butcher it up and put it back together or else end up with a low yeild.

The lack of a functional group anywhere near it has me thinking total synthesis would be the only way to get significant quantities.

 

[Curious Chemist]

it has me thinking total synthesis would be the only way to get significant quantities

I absolutely agree. Only total synthesis makes sense for THCP at this stage.

The 5-heptyl-benzen-1,3-diol building block is called “sphaerophorol” (because it was isolated from lichens of the Sphaerophorus genus) – hence the names of the corresponding CBD and THC analogues are “cannabidiphorol” (CBDP) and “tetrahydrocannabiphorol” (THCP).

The relative cannabinoid content in the original source (n-hexane extract of Italian FM2 strain) is extremely small, with 56 mg/g and 39 mg/g for CBD and Δ9-THC versus 243 and 29 μg/g for CBDP and Δ9-THCP (Citti et al. 2018 ; doi: 10.1038/s41598-019-56785-1). That means only 0.0029% of the total extract is THCP. Other strains have a THCP content of up to 0.015% ( Bueno 2020 ; doi: 10.1021/acs.jnatprod.0c01034 ). But even if no THCP-rich strain is ever identified… I’m sure that in a not so far future there will be genetically modified Cannabis with drastically increased Δ9-THCP content, considering that the required tools like CRISPR and site directed mutagenesis are already available and the market is large enough.

However, at this stage all Δ9-THCP is surely prepared by total synthesis... possibly following the published procedure ( Citti et al. 2018 ; doi: 10.1038/s41598-019-56785-1).

• sphaerophorol + (1S,4R)-p-mentha-2,8-dien-1-ol --> CBDP
• CBDP --> Δ8-THCP
• Δ8-THCP --> THCP-HCl-adduct
• THCP-HCl-adduct --> Δ9-THCP

That’s 4 synthetic steps and a lot of fractionations of complex mixtures. But even for a semisynthetic approach using the cyclization of natural CBDP, one would still need to fractionate more than 4 kg of the FM2 hexane extract for every 1 g of starting material and still have three synthetic steps do go – that is simply not a practical approach.

Consequently, as of today, users of THCP surely consume a fully synthetic compound (even if vendors falsely claim 100% natural!) - not that I believe that synthetic (or semi-synthetic) is in any way inferior to a natural product – it’s just that some people care a lot and value natural over synthetic compounds.