Just curious, has anyone attempted synthesis of THC-O-Phosphate? I was interested to hear that it had first been synthesized in 1978 in order to create a much more measurable and consistent method of providing doses in research applications due to it’s water solubility and therefore ability to be injected straight into the blood stream in highly controlled quantities. I realize you all probably think I’m trying to shoot up THC now, but that’s really not my goal with this. My goal is to understand what it would take to create a water soluble THC derivative that does not require microencapsulation, which would surely be a better method for liquid infusion than microencapsulation currently is.
Haven’t heard anything about it, let’s hope the chads don’t start trying to make this one because when you inject something, it’s a whole new ballgame. My synthetic background is so far removed for biology, I don’t know how to phosphorylate an alcohol; but if I were to guess, treat THC with strong base, LDA or sodium hydride, anything stronger will attack pi bond, calcium-chlorophosphate in a dry aprotic solvent; toluene, hexanes, THF, diethyl ether, take your pick, followed by protonation in the workup; standard organic workup (LLE wash, chromatography).
I’m not so sure THC phosphates would be water soluble but may be polar enough to self-emulsify into micelles.
Here’s my formal best guess for actual synthesis
Calcium chorophophate, diethyl ether, THC, Sodium hydride.
Liquid-liquid-extraction to extract calcium THC-phosphate (likely water soluble) from reaction mixture, adjust pH to get THC-phosphate in dianion form, wash with hexanes/ ethyl acetate to remove organic by products, then louche with ethanol or acetone (whatever solubilizes carbonate) to precipitate, wash with cold solvent. That would yield the dianion form which is likely water soluble/self-emulsifying.
How acid sensitive are the phosphate forms? I intentionally avoided acids because acid degumming cleaves phosphate esters, which complicates the work up.
Oh. I like the phosphoryl chloride better, nice hydrolysis. And it looks like the dianion is water soluble. Does the phosphate get cleaved once it’s in the body?
Bravo! I’m not sure anyone wants to test intravenous cannabinoid because shit, why would you? What about oral consumption? Is anyone brave enough to try it? Oral would likely be very safe because of phosphate cleavage upon entering the stomach. I’d be curious about taste if it was in water.
Emulsions are bitter for a number of reasons, one being micelles and detergents in general are bitter. I’ve heard CBD is also bitter, but just sonicating my emulsifiers without any bioactive, I get a transparent suspension of micelles, which yields a very bitter result.
This actually makes water soluble cannabinoids, and though they are chemically altered, they are relatively safe since the phosphate will get cleaved very easily!
How thermally stable is the phosphate ester? Does it dissolve in water after being heated to 90C?
I would guess they do since phosphate esters are usually stable up to 200C, but since it’s an aryl phosphate, with an ortho and para electron donating group, I wouldn’t be surprised if it was more susceptible to thermal degradation.
