Im looking at iso-THC, that structure is quite different and it looks like it would make some different fragments than d8/9-THC. Id doubt it would have a similar RT with the weird doublebond to iso group. I would not consider iso-THC a candidate for any of those peaks pictured.
Also looking at ABN-THCs with just the varian chain switched flopped aroundā¦ could see them being candidates. Would account for the larger RT shift seen on some of the byproducts. Also would fragment similarly.
The paper @kcalabs linked is wonderful. Itās the paper that spurred me to write about this recently but I had trouble finding it when I went to compile this post.
According to the literature, the cyclization reaction of CBD seems to occur following an acid-catalyzed activation of a specific double bond. 9,10 A dihydrobenzopyran ring moiety is formed by internal ether formation of one of the phenolic groups with one of the double bonds. The two double bonds in the CBD structure are responsible for the formation of two different compounds (Scheme 1). If the activation occurs on the Ī8 double bond, the products show the THC scaffold (Ī9-THC, path b); otherwise, the Ī1 double bond activation leads to the formation of the iso-THC scaffold (Ī8-iso-THC, path a). The latter cyclization is much less frequent. However, acidic conditions are responsible for further isomerization toward the corresponding thermodynamically more stable compounds, Ī8-THC andĪ4(8)-iso-THC, respectively. 11
So iso-THCs, like many candidates here, appear to be yet another side reaction that will occur in specific conditions, but not all reactions. This is the case with the ethoxy/methoxy THCs, oxygenated compounds, etc. pTSA and hexane notably does not appear to form iso-THCs. HHC appears to be an intermediate before forming the iso-THCs, so I likewise would not expect to see it present in a reaction with pTSA and hexane.
I remain skeptical on ABN THCs. I believe this is a stereoselective process as well so I donāt see it being the respective Ī8/9 enantiomers or cis-THC stereoisomers. In my limited understanding, these would need to form from other building blocks such as olivetol.
@Labdog My apologies if youāve already stated, but what catalyst/solvent was used in the sample you tested? I agree with what you said in regard to the structure but it looks like Ī8-iso-THC coelutes with Ī8-THC via HPLC in the paper KCA linked. And Ī4,8-iso-THC with Ī9-THC.
These would be various conditions from various cooks. But they are using hcl and sulphuric. The run pictured is a representation of the 60+ d8 conversions I have ran. All have these peaks, none have anything looking like HHCs. Allthe byproducts are at 315.
Yep, looking at their method, they are using about the same as me. Bunch of peaks all jammed up togetherā¦ So maybe isos are back onā¦ But are they going to fragment the same?
I see a different ring structure VS d9thc, like the two rings are sharing 3 carbs in the iso VS only 2 in the regthc.
Also that iso group on the top ring(these rings have names right?)ā¦ That is quite different than just the me group in regthc
Iām not sure they will produce the same fragments as ol d9ā¦ Which has been fragmented to hell by some awesome guys with a tofā¦ and Iāve traced all the fragments made by my d9 standards and all these byproducts tooā¦ Just no different sizesā¦ All fragments accounted for. Uhge inject vol and still nothing coming up different. I donno is there any fragment library for iso-thcs.
Talkin that sweet ms sauce, m/z me bro, Ms to the nā¦ I want to see all them fragmentsā¦ donāt give no shit bout decimal places neither
Ok uploading my modified THC fragmentation pathway I stole from a really good paper I cant remember right nowā¦ Please shout out the paper if you know it (pictured is D9, but D8 and enantiomers would produce exactly the same frags)
I have marked up the main fragments I generate by CID on my MS/MS, weights are noted for the main ones and highlighted the paths to themā¦ generally the 93 and smaller frags are only seen at high collision energies.
Now the question is, are these ISO-THCs even able to fragment the same? I am leaning twards no mainly because those 231 and 193 frags (which I see in the byproducts) look like they cannot come from the ISO structure and are specific to the ring structure of regTHCsā¦ Am I interpreting this wrong?
Cant rule out that the ISOs may be generating frags the same weight but different structures than the ones picturedā¦
This is an area Iām not as knowledgeable about so Iām going to wait for someone else to chime in. Again, not my wheelhouse, but is it really likely that they would be generating different fragments with the same weight? Intuitively Iām guessing no. If Iām understanding this correctly, these HAVE to be THC structures.
We have ruled out ā7 and ā10 THC because of different retention times compared to known standards. One of these peaks could still be exo-THC.
We have hypothetically ruled out stereoisomers. Unless my understanding of chemistry is seriously off, this reaction does not produce ā9 or ā8 THC stereoisomers.
And likewise, we have hypothetically ruled ABN THCs for a similar reason.
I donāt know whatās left. Is there some pathway to creating stereoisomers or ABN THCs that Iām overlooking? These are all enticing since I assume they would fragment in a near-identical manner to regular THCs. I feel like we would be seeing other breakdown products but itās not like I have a degree in this.
I def think enantiomers (sterio isomers) are in the candidate pool. From the waters paper I reposted: āThe main plant-derived stereoisomer is (-)trans-Ī9-THC, while many synthetic preparations of THC produce the more stable Ī8-THC isomer, or a mixture of positional and stereo isomers.ā
So Id think (+)trans-Ī9-THC and/or (+)trans-Ī8-THC would be the possible enantiomer byproducts from the CBD + acid reaction. They would definitely have the same fragments. The mechanism is thereā¦ its called chaotic friggn ring closure (pictured in scheme 1 of the JNatProd paper) ā¦ with no suitable aromatic solvents (looking at toluene) to direct this ring closureā¦ looks like you may get some weird ass stuff (ISOs for instance). Enantiomers would be the best scenario IMO because at least id think they are not super different (biochemically) than their counterparts.
Shit I got my papers mixed upā¦ iso formation pictured in that scheme 1ā¦ enantiomers formation not pictured but mentioned in waters paper.
I could be wrong, but I thought the synthetic preparations they were talking about are starting from olivetol. The other paper doesnāt seem to demonstrate the possibility of enantiomers? Nevermind seeing your edit as soon as I posted. Iāll double check but Iām pretty sure all the references point to this being a stereospecific reaction. The THC scaffold doesnāt ever change before Ī8/9 are created, just the position of the double bond.
Ok yes they are using standards and talking about āsynthetic preparationsā so probably starting from olivitol. They do a reaction on plant derived CBD and only make the (-) D8/9 THCs (normal stereo isomer). From the paper: āThe sample exposed to acidic conditions contained a significant amount of (-)Ī9-THC, calculated to be 1.16mg or approximately 7.6% of the initial 15.26 mg sample. There was also a very small detectable amount of (-)Ī8-THC in the sample exposed to acidic conditions. The samples were incubated for one overnight period (approximately 16 hrs), given more time the conversion would likely be even more pronounced.ā
So yes looks like that stero center is setā¦ im wondering if there is some mechanism that could still change those stereo centers during ring closing (even just on 1%) of the reactionā¦ double bond destabilized and maybe jumping around and to push of an H momentarily and then you get a different stero center? Jeez I was never good at that in ochem.
Same here. An H getting briefly pushed off seems a lot more likely than the molecule cleaving and reforming as an ABN THC butā¦ does that happen? There are probably better standards for the (+) enantiomers and cis isomers than the ABN-THCs so at least they should be a lot easier to rule out.
Yeah thereās always at least 3 unknown cannabinoids in a row with MW314. Shows up in CRCād extracts too along with a random low percentage of D8 (~2%). Thereās usually a few unknown cannabinoids in that mess but the three 314ās donāt seem to show up without some amount of D8 present.
