Mystery unknown from Trichocereus peruvianus

[moecat]

I obtained the above mass spectrum from a methanol/5% acetic acid extraction of a dried sample of this cactus.

It was the major component, at least 92% by weight.

No hits matched in the library and series dilution of the sample yielded a consistent mass spec for this unknown. It was also stable on exposure to high pH in acetonitrile.

My theory is this....It is a tetrahydroisoquinoline, specifically, o-methylpellotine.

I believe the mass spectum is indicative of the retro-Diels-Alder fragmentation of this structure:

Does anyone know of a link to a similar compound's mass spec for comparision?

moecat

 

[ROLLerskater954]

silly chap ! its elementary dear watson

 

[Blowmonkey]

It was the major component, at least 92% by weight.

That's really interesting. I can't help you though, sorry.

 

[Grignard]

Hmm, there's nothing in Beilstein about it? Can you get any NMR spectra on your unknown? Also I dunno if you have the ability or the authority, but can you synthesize an authentic standard and compare it against this?

 

[BilZ0r]

I really know nothing about chemistry beyond simple 1st year college stuff, but it strikes me as odd than a simple A/B extraction could lead to such a pure product... has something like that been shown before?

 

[moecat]

Hmm, there's nothing in Beilstein about it? Can you get any NMR spectra on your unknown? Also I dunno if you have the ability or the authority, but can you synthesize an authentic standard and compare it against this?

Yes, Yes...C13 NMR would be the way to go, but I would still have to sort through an intepretation, and a synthesis would be a lot more work. Just having some reference spectra of tetrahydroisoquinolines from the literature would be nice.

In the meantime, I'm left to ponder the interesting similarity between the major component's mass spec shown above and this minor component's mass spec:

Note difference of 14 m/z units for the M+ ion (251-14=237) and the most abundant fragment (70-14=56) , yet they share a common fragment of 181 mass units.

This appears to be a compound related to the major component but replaces a hydrogen with the a methyl group, i.e. a net change of 14 units.

Keeping in mind my proposed "retro-Diels-Alder fragmentation" pattern, I would assume the 181 fragment appears from the trimethyoxy isoquinoline structure and the difference occurs on the right-hand side of the molecule....that is, the minor component is the O-methyl derivative of either of these two compounds:

While the unknown in question is related to the major component O-methylpellotine (MW 251) by having a hydrogen substitute for one of the methyl groups (MW 251-14=237), it is NOT pellotine,

For it were, it would NOT produce the 181 m/z ion indicative of a trimethoxy substituted compound.

Having a reference mass spec of any of these isoquinolines would be nice to have for comparison....I haven't been able to find one yet

 

[moecat]

I really know nothing about chemistry beyond simple 1st year college stuff, but it strikes me as odd than a simple A/B extraction could lead to such a pure product... has something like that been shown before?

Very much a surprise considering the common assumption that mescaline is the basis of the activity of this species. I certainly now take the comments of others who talk about the effects of mescaline based on their experience with this plant with a little bit more skepticism.

The total ion chromatogram is shown here:

There are several minor components, such as the one I discussed above, but this unknown component was over 90 area percent. I will say this extract was worked pretty hard including a pentane 'defatting step' and copious amounts of activated charcoal for clean up.

I have no idea whether such a thing has been shown before, and was one of the reasons I thought I'd post it in this forum. This sample was from a commercial source of dried plant tissue...based in the UK.

 

[nuke]

Hmmm...what do we know about the activity of the above suspected compounds? This thread makes me wish I'd picked up Sasha's new book on isoquinolines...

 

[phase_dancer]

Having a reference mass spec of any of these isoquinolines would be nice to have for comparison....I haven't been able to find one yet

So far I haven't had much luck but here's Anhalidine, taken from:

Alkaloids from Neobuxbaumia species (Cactaceae) by C.M. Flores Ortiz, P.Da vila and L.B.H. Portilla; published - Biochemical Systematics and Ecology 31 (2003) 581–585

 

[moecat]

So far I haven't had much luck but here's Anhalidine, taken from:

Alkaloids from Neobuxbaumia species (Cactaceae) by C.M. Flores Ortiz, P.Da vila and L.B.H. Portilla; published - Biochemical Systematics and Ecology 31 (2003) 581–585

This must be chemical ionization data of some kind. I can't explain such a large M-1 peak otherwise.

Here's Analidine:

In an electron impact ionization spectrum, I would guess this fragment perhaps....

while the trimethoxy compounds would give a mass 181 fragment (as shown in the two mass spectra for the unknowns in the cactus extract.)

Perhaps I'm completely wrong on this...without looking at more reference spectra, I find it hard to say. The technique I used was electron impact ionization, and I don't think I can compare chemical ionization mass spectra.

Basically, this is as far as I can get.

I think my assumption of a large molecule falling into two primary fragments in a decyclization step is reasonable. One fragment would be the aromatic ring with various degrees of methoxy substitution and the other fragment would be the amine portion eliminated in the decyclization. This is the case for the tetrahydro-beta-carbolines as described here.

A similar paper discussing the tetrahydroisoquinolines would be neat to find.

Shulgin's book "The Simple Plant Isoquinolines" is not of much help. It doesn't discuss mass spectra of these compounds.

It does have a nice forward that clearly indicates the phenethylamines and tetrahydroisoquinolines are related by ring closure in the same way that tetrahydro-beta-carbolines are related to tryptamines by ring closure.

Thus two classes of compounds seem to come in pairs....PEA's/isoquinolines ...tryptamines/b-carbolines.

 

[Grignard]

Here's a little snippet from an article I found.

If you want to go look at the full article, the ref is:

J. Am. Chem. Soc. Vol 91;Jun 1969;3682-3685
Chemical Ionization Mass Spectrometry of Complex Molecules

 

[moecat]

Here's a little snippet from an article I found.

If you want to go look at the full article, the ref is:

J. Am. Chem. Soc. Vol 91;Jun 1969;3682-3685
Chemical Ionization Mass Spectrometry of Complex Molecules

Well, then my assumption is wrong! This doesn't match the 251, 181, 70 pattern of the major component.

So what is the stuff I extracted? I get extremely poor library matches for the spectrum. What would have a molecular weight of 251, and break into two major fragments i.e. 251 -> 181 + 70?

And How is it related to the minor component with a MW of 237? A molecule that has the fragmentation pattern of 237 -> 181 + 56

Is it a demethylated version of the major component?

Hey, I really appreciate the link and reference! I've been wanting to see the EI mass spectrum of O-methylpellotine for the past 6 months.

The link shows my guess to be incorrect.

 

[fastandbulbous]

Is it possible that what you've got is an artifact from the method of extraction? It's possible that one of the reagents could form, in one way or another (or have as a minor impurity), an aldehyde that would lead to a variation of a Mannich condensation. Phenethylamines and tryptamines are quite prone to it at room temp conditions; as it happens more often with tryptamines to give beta-carbolines, the details are in the post about unusual compounds from Mimosa hostilis (this post).

Hope it's of some help

 

[moecat]

Yeah, but since my guess of O-methylpellotine isn't correct, then what is it?

What else has a MW of 251 that could be formed by this reaction? If you try and think of all the tetrahydroisoquinolines that have a MW of 251, how many possibilities are there? I can think of just one ....and it isn't it!

 

[fastandbulbous]

On that bit, your guess is as good as mine. I've been trying to match structural formulas to MW's and I'm at a loss as well.

Ah, just thought; could it be a quaternary base (two methyl groups on the isoquinoline nitrogen) - they'll give strange decomposition products. I'll have a look in a couple of text books and get back if I find any possible candidates.

Good hunting

 

[Smyth]

An alternative mechanism of the Pictet-Spengler reaction is attached below. This is a variant of the Bischler-Napieralski reaction that uses an aldehyde instead of a acylating agent. It is facilated by electron donating groups such as methylenedioxyl on the benzene ring. We'll have to wait and see what Shulgin has compiled for us before bioactivity data springs to light.

 

[Smyth]

The above alkaloid is related to Lycorine that is found in daffodils. Sorry to dump this on you since it is not really concentrating on the job at hand. it was a subject glanced at in my 4th year biosynthesis module last year.

 

[moecat]

The above alkaloid is related to Lycorine that is found in daffodils. Sorry to dump this on you since it is not really concentrating on the job at hand. it was a subject glanced at in my 4th year biosynthesis module last year.

I think any conjecture about the identity of the unknown needs to at least possibly agree with above mass spec data.

I don't believe Lycorine agrees with the mass spec data. It's MW is 323, and I have a feeling its mass spec would be more complicated than the 251, 181, 70 pattern of the unknown.

This unknown showed this consistent mass spectrum under three dilutions and exposure to high pH. Scans out to 550 amu didn't give any indication of a molecular weight above 251 either.

I was wondering more whether it could be an acetylated mescaline derivative. The extraction was done in methanol/5% acetic acid and after the extraction, the methanol was boiled off until the temperature suddenly rose to above the boiling point of methanol. The residue at this point was a thick liquid with a pugent acetic acid odor. It was worked up from there.

Even considering acylation and various methyl isomers of mescaline, I can't seem to arrive at a possibility that agrees with the mass spec data. The high pH experiment didn't indicate that the unknown was an acylated derivative...while it did for a one of the other trace components.

I'm perhaps misguided to believe the two mass spec shown would arise from a decyclization reaction of two compounds that are related by a methyl group. That's the crux of the rationalization that gave O-methylpellotine.

 

[fastandbulbous]

If you're thinking that it might have something to do with acetylated alkaloids, is it possible that it could be O-acetylation of a phenolic OH group? It seems that some of the isoquinolines have an hydroxy group at position 8, rather than a methoxy

 

[moecat]

Also a number of acetyated PEA's are possible. I just never have come up with two that have molecular weights of 237 and 251 and would share a common 181 fragment. It's like a riddle where you can play a lot of what-if's and sum up the masses.....but I haven't found the solution yet.

There were a few other components pretty well identified in the material...a dimethoxy PEA, and an acetylated derivative (data I haven't shown). It's like the mass spec drew a blank on these two components. So it's the failure of the identification within the context of clear successes that is also odd....allowing elimination of a number of possibilities and confirmation that that there was nothing particularly wrong with the analysis.