Aeruginascin or N,N,N-trimethyl-4-phosphoryloxytryptamine is an indoleamine derivative which occurs naturally only within the mushroom Inocybe aeruginascens.[1][2] Aeruginascin is the N-trimethyl analogue of psilocybin. It is closely related to the frog skin toxin bufotenidine (5-HTQ), a potent 5-HT3 receptor agonist, and has been found exclusively in Inocybe aeruginascens.-Wikipedia; https://en.m.wikipedia.org/wiki/Aeruginascin

N,N,N-trimethyl-4-phosphoryloxytryptamine caught my attention as soon as I discovered it, I was curious about one or two things regarding it though:

Sorry if this sounds like a soft-headed question, but,
Since nitrogen only has three gaps in its atomic shell, and since one gap is filled by the two-carbon side-chain and the other two gaps are occupied by methyl groups, then how is this third methyl substitution connected to the amine nitrogen?

My other questions were regarding any good sources of literature or research involving this compound, I'm always fascinated by tryptamine compounds, and a 4-substituted (4-phospholoxy) tryptamine that is being produced by a single species of fungi is certainly something that I feel is worth looking into, any leads or information would be much appreciated, thanks,

-EG

A real chemist will be able to answer your questions more appropriately, but I think quaternary ammonium salts do not pass the blood brain barrier so it probably isn't psychoactive.

https://en.m.wikipedia.o...aternary_ammonium_cation

This link really helped

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Activity was not my concern here.

(Though N,N,N-trimethyl-4-phosphoryloxytryptamine does have some receptor agonism at 5-HT3, so while it may not be mind altering it is pharmocologically active.)

As a youth I was always fascinated with forming "chemical chimeras", where I would combine in structure two known compounds, I always thought that if you could add another methyl group to the nitrogen 6 of LSD you would create a molecule of DMT burried within the LSD molecule (Starting from the benzene ring, then over to the pyrrole ring, then follow the two carbon bridge to a nitrogen with a methyl group connected to it (position 6), you have just outlined the NMT within LSD) since nitrogen only has 3 gaps in its atomic shell, it's not possible to add another methyl group, or anything for that matter, to this nitrogen, thus destroying my concept, I mean You could cleave off the whole top half of the LSD molecule to free up a gap in nitrogen 6, as was done with RU-28306 ( https://en.wikipedia.org/wiki/RU-28306 ) , though this fundamentally changes the structure of the starting molecule, and would not fit into my concept.


It was seeing 3 methyl groups off an amine nitrogen connected to a two carbon side chain that caught my eye here...

I'm sure this concept (LSD/DMT structure combination) is a waste of time, had there been a viable compound here I'm sure Hoffman would have realized it, it's still a fun idea though.

I'm only in my second year of organic chemistry, so I still have a good deal to learn, so sorry if these questions seem soft-headed or ill-thought. since I refuse to publicly state my interest in psychedelics in an academic setting, I don't have many places to ask these questions.

I'm still fascinated by N,N,N-trimethyl-4-phosphoryloxytryptamine regardless, it's a novel natural tryptamine, it's related to active tryptamine compounds, and occurs in a fungi, to me anyway, this is enough to warrant further investigation.


-EG

Are there other examples of Quaternary ammonium cation homologues of other tryptamine compounds?

-EG

Bufotenidine

Here's an article on some of its effects:
Blockade by bufotenidine of the serotonin- and narcotic-analgesics-induced contraction of dog intestine in vivo.
L.F. De Oliveira, A.D. Bretas
http://www.sciencedirect.com/science/article/pii/0014299973901404

The 6 nitrogen is already has two hydrocarbon substituents - one is free (and obvious), and the other is part of a six-membered ring. It's not a methyl group exactly, but from a structural perspective, it's good enough. When looking at the active site of the 5-HT2Ar, the dimethyl substitution on the amine actually causes steric hinderance, meaning that DMT cannot form the same hydrogen bonding pattern that serotonin does. Since it's that steric effect that causes partial agonism, other substitutions, like what you see in the top half of LSD are probably just as effective.

The presence of the carbonyl group in LSD also allows it to interact with an asparagine amino acid that normally 5-HT and substituted tryptamines don't, which may contribute to it's unique effects. At the end of the day, I think freeing up that second methyl group would be a waste, especially if it cost you the carbonyl group.

Check out the attached paper for more.

Blessings
~ND

This is theoretically possible and would also result in the formation of a quaternary ammonium compound.

It would certainly be interesting to see if aeruginascin shares pharmacological properties with bufotenidine.

What has fascinated me since I first read reports about aeruginascin, is its purported synergistic effect with psilocin: Dr. Shulgin wrote:

The reports appear to be highly anecdotal, it would be nice to have more information. I can sucessfully recognize determine ps. semilanceata, but personally, I would not dear to pick and eat any inocybe species, knowing that many inocybes contain dangerous amounts of muscarine.

There is a possibility of competitive inhibition of metabolic pathways. It's all waiting to be studied!

Pharmocologically I really don't see any point in the DMT/LSD chemical chimera, my fascination is purely structural.

If you start at the benzene ring of LSD, then move right to the pyrrole ring it's connected to, then follow the right side of the molecule (2-carbon bridge) to a nitrogen with a methyl group attached (position 6) you would have out-lined a molecule of NMT burried with in the structure of LSD...

Now, my concept was to have two methyl groups on the nitrogen 6 of LSD, thus converting the burried NMT into a burried molecule of DMT.

Now, since there are only 3 gaps in the atomic shell of nitrogen, and two of these gaps are part of a ring structure and the last available gap has a methyl group in it, it would not be possible to add anything to nitrogen 6 as all available gaps in its atomic shell have been filled...

But imagine if there were one more gap, and a second nitrogen could be added without disrupting the ring structure, you would be able to convert the already present burried molecule of NMT into DMT...(Though this is not possible, the idea is flawed by the limit in gaps to the atomic shell of the nitrogen atom)

With the compound RU-28306 they added a second methyl group to nitrogen 6, but at the cost of removing a ring structure to free up a gap in the shell of the nitrogen atom...


With 6-ethyl-6-nor-lysergic acid diethylamide (ETH-LAD) the second methyl group was connected to the methyl group already present forming an ethyl chain, and though the concept with ETH-LAD has nothing to do with what I'm talking about, it would have been the closest viable solution to putting two methyl groups on nitrogen 6...

Still, seeing the quaternary ammonium cation tryptamine compounds somehow reminded me of this "LSD/DMT chemical chimera" concept, which I know is flawed, but it's still fairly fun to contemplate, what if there was a solution involving a quaternary ammonium cation at position 6 which could then have another methyl group connected? ....this is all just wild brain-storming though, and I'm sure very little of it is applicable to real world chemistry...


-EG

Fascinating stuff! Thank you for that bufotenidine link!

I'm particularly interested in this compounds (N,N,N-trimethyl-4-phospholoxy-tryptamine) purported synergistic effects with psilocin as well as the Inocybe aeruginascens fungi from which it is derived. I'm going to for sure be doing much more research regarding these topics.

(The toxic inocybe species "Inocybe erubescens" does contain high amounts of muscarine (as do other inocybes), which can be deadly when consumed in large amounts, but this is not a typical deadly fungi poison such as alpha-Amanitin, which causes organ failure and death. Muscarine is one of the key compounds present in amanita muscaria and can be consumed with caution. Though this shouldn't be an issue as a responsible mushroom Hunter will always wait for 109% conformation on an ID before consumption. Though These species should be easily distinguished from one another, If not in the field than in the lab. I'm confident enough in my mycological identification abilities that I would feel comfortable seeking out this species, though I have no plans to do so. ( wild mushroom hunting is not to be taken lightly, the risks are very real, and sufficient knowledge is required)

Thank you again for the information, really fascinating stuff!

-EG

https://upload.wikimedia...ic_acid_molecule.svg.png

Ok, it would not let me save the picture and post it here, which is a bummer, because it perfectly outlines the molecule of NMT burried within Lysergic acid (left) and N-methyl-phenethylamine burried with in LysergiC acid(right)

(Just imagine a nitrogen with two ethyl groups connected to it in the place of the hydroxy group off the carbonyl for LSD molecules in place of lysergic acid molecules)

-EG

Muscarine is deadly in sufficient amounts and should not be underestimated or played with wantonly! Even though muscarine poisoning is easier to treat and has better recovery than amanitin poisonings, failing to diagnose or treating too late can still be life threatening.

BTW, coincidentally, muscarine is a quaternary amine, just as aeruginascin.


Actually it is only present in trace amounts in amanita muscaria. Its main toxins are ibotenic acid and muscimol, and these can be leached out quite easily by boiling in plentiful water and draining. I've done this many times and consider these mushrooms a gourmet delicacy, much to the surprise and amazement of many people who have been conditioned to believe that this mushroom is deadly and should not even be touched.


Be careful and don't rush in where angels fear to tread. Here is what wikipedia has to say about inocybe toxicity:

Wikipedia further lists several inocybe species as containing psychoactive substances, but does not say whether these do also contain dangerous amounts of muscarine or not. The latter case should not be blindly assumed.


As the saying goes: all mushrooms are edible, but some only once.

Not only should one be able to determine a specific mushroom in all its variable appearances, one should also be able to know which lookalikes exist and be able to determine these in all their variable appearances.

Be careful!

I know you can find the structure of DMT embedded (or at least, partially embedded) in LSD. You can also find methamphetamine, if you look hard enough.

The point I was trying to make is that it doesn't matter if the methyl group attached to the amine are terminal, or part of a larger structure because, even in a compound like DMT where both methyl's are terminal, the only purpose they serve is to cause steric hindrance, and stop that amine from bonding with Ser3.36. That's (apparently) why partial agonism occurs, as to the full agonism caused by 5-HT: the interaction between the amine on the tail and the serine is too weak, thanks to those hydrocarbon groups. Because it's a steric interaction as opposed to an electronic one, exactly what it is that's causing the hindrance shouldn't matter as much.

Check out the partial agonism paper, it's pretty interesting stuff.

Blessings
~ND

(In response to ND) I completely get what your saying, and I'll admit pharmacology is not one of my strong points, I'm an organic chemistry student, and my interest here was purely structural, (I don't mean to sound like a pretentious nit-picker here, but it's a N-methyl-phenethylamine moiety found in LSD, it's a methyl group short of meth amphetamine), I'm completly certain that pharmocologically it would be a useless endeavor to put two methyl groups on nitrogen 6 of LSD, but structurally it creates a burried DMT moiety within the compound, which was the initial concept.

(Position 6 on LSD is a pharmocologically "hot" spot to tinker with, the xxx-LAD series involves dealkylating nitrogen 6, giving nor-LSD, then adding alkyl substituents to nitrogen 6, altering its pharmacological action, so, an ethyl group at nitrogen 6 Gives ETH-LAD, a propyl chain gives PRO-LAD, ans allyl chain gives AL-LAD, etc...
So I'm sure my concept compound would still have some interesting activity, though as I said, pharmacology is not one of my strong points, I'm a chemistry person.


The pharmacological information you mention does interest me, it was just some what peripheral to the initial concept...

It was novel moiety combination in structures of known compounds that was fascinating to me.

This is the shared pharmacology of the psychedelics as I understand it, though there is partial agonism here and there, which I'm sure is mentioned in your paper, which I can't get to work (I'm on an old device)

·psychedelic phenethylamine compounds ( 5ht2a and 5ht2c receptor agonism)

·psychedelic tryptamine compounds ( agonism at 5ht1a + 5ht2a + 5ht2c )

Then there's LSD (5ht1a + 5ht1b + 5ht1d + 5ht2a + 5ht2c + 5ht5a + 5ht6 + 5ht7 + d1 + d2 + d3 + d4+ Alpha-2 )

David E. Nichols says LSD has "rich" pharmacology due to the many receptor sites it's agonizes, fascinating stuff...

I'll look into that paper, I'll try to find a way to get it to work.

This link (below) shows the N-methyl-phenethylamine moiety (right) and the mono-methyl-tryptamine moiety (left) burried within LSD

https://www.anoniem.org/...ic_acid_molecule.svg.png

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I was researching quaternary ammonium cation compounds in relation to DMT when I came across shulgins methods for synthesis of DMT:

(He is creating a quarternary ammonium cation of DMT (N,N,N-trimethyltryptammonium iodide) with tryptamine and methyl iodide, and then demethylating it into DMT!

Here's the entry from TIHKAL:

SYNTHESIS : (from N,N,N-trimethyltryptammonium iodide, dimethyltryptamine methiodide, DMT·CH3I): This quaternary salt is prepared from tryptamine and methyl iodide. To a stirred solution of 3 g tryptamine in 30 mL IPA there was added 10 g methyl iodide. Cream-colored solids appeared immediately and, after 12 h stirring at room temperature, these were removed by filtration, washed twice with IPA and warm isopropanol, and air dried to constant weight. There was thus obtained 1.81 g N,N,N-trimethyltryptammonium iodide. Recrystallization of an analytical sample using acetonitrile gave a white crystalline product with a mp of 210-211 °C. IR (in cm-1): 767, 919, 953, 978, 1105, with a sharp stretch at 3400. In principle, DMT is contained in the filtrate along with NMT and tryptamine itself. The tryptamine can be removed based on its ether insolubility and the NMT by its conversion to the benzamide with acetic anhydride or benzoyl chloride. The remaining basic material is largely DMT which can be further purified as the picrate salt. The yield is minuscule, and better results are obtained by the demethylation of this salt.

The demethylation of the iodide salt: Under an inert atmosphere, a solution of 0.40 g N,N,N-trimethyltryptammonium iodide in 5 mL THF was treated with 1.5 mL of 1M LiEt3BH in THF and held at reflux temperature for 9 h. After cooling, the mixture was acidified with dilute HCl and the THF removed under vacuum. The residue was suspended in dilute NaOH and extracted with Et2O. The extracts were pooled, and the solvent removed under vacuum to provide a residue of 0.12 g N,N-dimethyltryptamine (DMT) as a crystalline solid, with a mp of 57-59 °C. IR (in cm-1): 732, 740, 811, 859, 1011, 1037, 1110, 1171. The MS is discussed below.

The demethylation of the chloride salt: A hot aqueous solution of N,N,N-trimethyltryptammonium iodide was treated with an excess of freshly precipitated AgCl, and all was boiled gently for 15 min. The mixed silver halides were removed by filtration, and the filtrate stripped of H2O as rapidly as possible. To the residue there was added a small amount of MeOH follow by acetone until the crystallization of N,N,N-trimethyltryptammonium chloride was complete. It had a mp of 193 °C (80%), and it is considerably more water soluble than the starting iodide. This salt was pyrolysed under hard vacuum and the residue distilled. This distillate was dissolved in a small amount of methanol and acidified with dilute nitric acid. A small amount of insoluble material was removed by filtration, the aqueous phase washed with CHCl3, made basic with aqueous NaOH, and extracted with CHCl3. The solvent was removed under vacuum, and the residue treated with a hot solution of picric acid. This was decanted from a little insoluble material, and slowly cooled to provide the picrate of DMT as yellow needles with a mp of 167 °C. An aqueous suspension of this picrate was made basic with an excess of aqueous NaOH, extracted with Et2O, and the solvent removed under vacuum to provide a pale yellow residue that crystallized. This was pressed on a porous plate and washed with petroleum ether to give N,N-dimethyltryptamine (DMT) as an off-white solid with a mp of 47 °C.

The demethylation of the thiophenolate salt: A suspension of 2.5 g N,N,N-trimethyltryptammonium iodide in 25 mL MeOH was brought into solution by heating, and treated with 1.0 g Ag2O. The mixture was heated for 10 min on the steam bath, the solids removed by filtration and washed with an additional 20 mL MeOH. The methanol solutions were treated with 1.0 g thiophenol and the solvent was removed under vacuum. The resulting viscous oil (2.12 g) was heated with a flame to the reflux point and there was extensive bubbling. After 5 min, the light colored reaction mixture was cooled to room temperature, dissolved in 50 mL CH2Cl2, and extracted with two 25 mL portions of dilute HCl. These were pooled (pale yellow color), made basic with 5% aqueous NaOH and extracted with 3x25 mL CH2Cl2. After removal of the solvent from the pooled extracts, the residue (an amber oil, 1.04 g) was distilled at the KugelRohr. A white oil distilled over at 130-140 °C at 0.1 mm/Hg, and crystallized spontaneously. This distillate weighed 0.77 g, and was recrystallized from boiling hexane after decanting the solution from a small amount of insolubles. There was thus obtained 0.40 g of dimethyltryptamine (DMT) with a mp 67-68 °C. The distillate contained about 3% of 2-Methyl-1,2,3,4-tetrahydro-b-carboline (parent peak mass 186, major peak mass 186) as an impurity which was lost upon recrystallization. -shulgin; TIHKAL

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This is getting to long so I will respond to other posts in another post.

-EG

I had muscarine and muscimol mixed up in the post where I mentioned amanita muscaria, thanks for clarifying, but I would still not be as concerned as I would with alpha-amanantin containing species.

Muscarine is a quarternary amine, that's crazy, They (compounds found in amanita muscaria) almost look like phenethylamine compounds only the benzene ring was swapped out with a furan ring, muscarine, muscimol, and ibotenic acid are like this, fascinating stuff.

I understand your concern, though I assure I'm very well educated in mycological matters, and as I said before, any good mycologist or mycophagist will have to be 100% on the ID before consumption even becomes an option, also, I know how to examine spores under a microscope and I know how to identify fungi by taxonomic features as well as features involving where and what it was growing on and during what season, and I always research potential look alikes before a hunt, though in many cases I will already have a good deal of information on other fungi that grow in the same environment as fungi I have interest in. I have spent many years hunting wild mushrooms, and I have taken many mycology courses, and so on (I would never try to attempt a risk oriented endeavor without the proper education and preperation) though in this case I would only want to find this fungi for research purposes, and as I said before, I have no intentions of seeking out this fungi.

Fascinating stuff though...

-EG

I also found a good deal of tryptophan similar compounds with three methyl groups on the amine nitrogen, these compounds are derived from sea invertebrates...

Plakohypaphorines are iodine-containing indole alkaloids named for their similarity to hypaphorine, another alkaloid related to the amino acid tryptophan. First reported in the Caribbean sponge Plakortis simplex in 2003, plakohypaphorines A-C were the first iodine-containing compounds based on the indole ring structure to be discovered in nature. Plakohypaphorines D-F, also found in P. simplex, were reported in 2004 by a group including the researchers who discovered the original plakohypaphorines.-Wikipedia

·7-Iodo-N,N,N-trimethyltryptophan
·6,7-Diiodo-N,N,N-trimethyltryptophan
·5,7-Diiodo-N,N,N-trimethyltryptophan
·5,6-Diiodo-N,N,N-trimethyltryptophan
·5,6,7-Triiodo-N,N,N-trimethyltryptophan
·Etc,etc,etc....

-EG