Complex Indole Alkaloids ('Hyper-Tryptamines'?) from plants

[nen888]

..i initially began pondering the mysterious Mimosa hostilis alkaloid yuremamine

in What are the current views, facts and theories on DMT-N-OXIDE? - DMT Discussion - Welcome to the DMT-Nexus(see posts #11 and #13 for detail and refs) .. endlessness noted that it contains within it a DMT molecule..it is broken down into constituents by heat and basic conditions, thus not present in most tests & extractions, but i wondered if some (or all) of the DMT in the plant (after basic extraction) is in fact derived from the yuremamine 'hyper-molecule'..as it is suspected of MAOI and psychoactivity, this could explain the traditional 'Jurema' drink made without MAOI plants having activity, if made with only cold water techniques..

thinking about how molecules could reside inside larger molecules, i came across two interesting references..
..according to S. Voogenbreinder's Garden Of Eden, Psychotria beccaroides (from New Guinea), P. forsteriana (Vanuata), and P. lyciiflora and P. oleoides (from New Caledonia) contain:

complex indole alkaloids called Psychotridines - NMT-derived alkaloids made by linking 2-8 pyrrolidinoindoline groups. They are potently cytotoxic against rat hepatoma & human leukaemia cell lines, inhibit platelet aggregation, and are antibacterial, strongly sedative and analgesic in mice (CSIRO 1990; Janic et al. 1999; Saad et al. 1995)

The Australian shrub Hodgkinsonia frutescens (Rutaceae) ..contains a complex tryptamine-derived alkaloid..called hodgkinsine. Given orally to mice, 25-50mg/kg produced mild sedation and loss of balance..

hodgkinsine is found in the south american Psychotria colorata (with tradtional medicinal usage), and has also been found to act as both a mu opioid agonist and an NMDA antagonist [Amador et al. "Antinociceptive profile of hodgkinsine" Planta Medica 2000 Dec.] the bioactivity, like the molecule, is comlplex..

wikipedia says:

Hodgkinsine is a 'trimer' composed of three pyrrolidinoindoline subunits, with the monomer closely resembling another alkaloid eseroline which has similar bioactivity. Due to it's complex structure and multiple chiral centres, hodgkinsine has many stereoisomers and significant research has been undertaken to elucidate the structure-acticity relationships of the various isomers..

it should be noted that in bio-assay experiments the 'psychotropic effects' are either de-emphasised or hard to judge..'sedation' or 'loss of balance' in mice could mean a lot of possible different things..thankfully their medical value seems confirmed and growing..

this opens up a whole new world of cold-water extraction 'hyperloids' with all sorts of possible effects and possible manipulations,
& old world lost usages of the Jurema or 'Ajuca' sacred drink..
..not to mention ideas about how alkaloids transform and disguise themselves within plants


for more on yuremamine see:
Vespålåinen, J.J. et al. "Isolation and characterization of yuremamine, a new phytoindole." Planta Medica 71 1053-1057

here are the structures of hodgkinsine, yuremamine & psychotridine:

 

[nen888]

..fixed image of psychotridine last post, for more on it see:
Pyrrolidinoindoline Alkaloids from Psychotria oleoides and Psychotria lyciiflora
.

 

[Simon Jester]

I have had some really interesting stuff creep from an unheated, unbasified MHRB slurry. It's totally psychoactive in LARGE doses. Don't know what it is, not much else to tell at this point.

 

[endlessness]

Very interesting thread nen, thanks for contributing!

I am fascinated at the possibility of different isomers with unique psychoactivity. I wonder how does it work with the plant's biosynthetic pathway, creating these compounds, if stereoisomers are common in same species.

Also, regarding if DMT could originate from a more complex form, isnt it more reasonable that it starts at simple and goes more complex? Tryptophan->Tryptamine->DMT (and then -> whatever else -> yuremamine ?) Maybe our experts should give their input, I dont know how yuremamine fits in, how its biosynthesized. Im also very interested what would be it's breakdown products (in heat and basic conditions, as well as human metabolism)

Regarding oral activity of jurema, indeed its pretty clear that yuremamine is responsible for the oral activty, considering it's structure could prevent MAOI breakdown, and also considering it is unstable exactly to the condition that make jurema inactive orally (heat). It's also sensitive to bases so extracting conditions also break it down even if without heat. An alcohol soak could extract it though.

BTW here's the Callaway yuremamine paper:

Scientific Articles on DMT/Ayahuasca/Psychedelics - DMT Discussion - Welcome to the DMT-Nexus

 

[Hyperspace Fool]

Hyper-tryptamines...

We can only hope that some inspired folks take up this torch. Yuremamine extraction and cold water infusions of Jurema have intrigued many of us since we first became aware of the possibilities.

One novel concept:

Perhaps we can learn from the natural hyper-tryptamines, and create some of our own. There should be a large variety of such compounds that we could easily create artificially. They could be the next wave of RC's. Pure n,n DMT delivered in an orally active form... with built in RIMA activity. Cheap, legal, and in a compact, efficient compound!

No need to overharvest our rare botanical friends. No need to be shipping kilos of rootbark to our doors, with all the concurrent environmental costs of jetfuel.

They could be engineered for ideal purposes. A hyper-tryptamine optimized for snuff (buffered and PH balanced perhaps). One for smoalking. One for oral. One for enemas, etc.

Some crafty chem students could make a mint off of this idea.

 

[endlessness]

Hmmm, interesting idea hyperspace Fool, but considering the complexity of those substances, shouldnt it be the inverse, that they are very hard to synthesize? I mean, considering how simple DMT is, and still the fact that its not easy for people to synth with simple/unwatched chems, imagine a substance such as yuremamine, plus all the instabilities that must be a pain to synthesize, no? (though I know you were speaking beyond just yuremamine)

I was thinking that going back to the idea of someone in the position to do so, genetically modifying yeast to produce DMT, and then spreading the yeast around the world, to solve the (very apropriately mentioned) issue of having to ship many kgs of plant material around the world with all the costs it supposes. That would all be ideas for another thread though. Though one small note, mimosa hostilis, at least in brazil, is by no means rare or endangered or overharvested due to us. If anything, the 'common' use for mimosa (for fence wood and for burning) is much more endangering to the species (and widespread) than our use for it.

In any case, back to hyper tryptamines, regardless of how viable/easy it is, what you said, hyperspace fool, indeed raises TONS of interesting questions and possibilities, regarding all these unexplored compounds that could be present in nature or not, but that could have very interesting psychoactive effects! We need to explore moar

 

[Hyperspace Fool]

Hmmm, interesting idea hyperspace Fool, but considering the complexity of those substances, shouldnt it be the inverse, that they are very hard to synthesize? I mean, considering how simple DMT is, and still the fact that its not easy for people to synth with simple/unwatched chems, imagine a substance such as yuremamine, plus all the instabilities that must be a pain to synthesize, no? (though I know you were speaking beyond just yuremamine)

I was thinking that going back to the idea of someone in the position to do so, genetically modifying yeast to produce DMT, and then spreading the yeast around the world, to solve the (very apropriately mentioned) issue of having to ship many kgs of plant material around the world with all the costs it supposes. That would all be ideas for another thread though. Though one small note, mimosa hostilis, at least in brazil, is by no means rare or endangered or overharvested due to us. If anything, the 'common' use for mimosa (for fence wood and for burning) is much more endangering to the species (and widespread) than our use for it.

In any case, back to hyper tryptamines, regardless of how viable/easy it is, what you said, hyperspace fool, indeed raises TONS of interesting questions and possibilities, regarding all these unexplored compounds that could be present in nature or not, but that could have very interesting psychoactive effects! We need to explore moar

I suppose the viability of synthing these puppies will have to be tested by people who have the time, ability and inclination.

One idea would be to extract DMT or synth it in a lab, and then add on the extra rings or compounds. The resulting molecule would be legal, and I seriously doubt if anyone could give you too much shit for momentarily creating DMT (especially if they had no idea how you made your hyper-tryptamine). I won't even talk about how ridiculous the scheduling of such an omni-present alkaloid is.

It could be that one could get to the hyper-tryptamines directly from an indole or even tryptophan. Perhaps one could take 5-HTP and alter it into the correct shape while simultaneously adding the relevant "booster" sections.

I'm no chemist. But it does seem doable... AFAICT

 

[nen888]

..thank you for your responses Simon Jester, endlessness, & Hyperspace Fool..

yes, i'm also hoping some more knowledgeable of chemistry can offer some ideas..
i'm also interested in what the possible degradation products could be..

..endlessness, thanks for clearing up the reference

regarding if DMT could originate from a more complex form, isnt it more reasonable that it starts at simple and goes more complex? Tryptophan->Tryptamine->DMT (and then -> whatever else -> yuremamine ?) Maybe our experts should give their input

regarding your.. simple-tryptamine>substituted tryptamines & so on..idea..
i wonder if it is also possible that, in human blood & various organ bio-synthesis, DMT and other substituted tryptamines further evolve into yuremamine-like higher molecules
..could these have been missed in sampling of human urine and blood due to the technique (e.g. basic, GCMS etc), or they're only in the brain, or perhaps not yet looked for in detail..maybe our model of neuro-chemistry is too reductionist, hence not looking at hyper-complexs yet..?

I have had some really interesting stuff creep from an unheated, unbasified MHRB slurry. It's totally psychoactive in LARGE doses. Don't know what it is, not much else to tell at this point.

..Simon Jester, that's really interesting about the cold brew..how long was the plant material in solution for? how large is a 'large' dose, and what was it like..?


some possible experiments with MHRB for yuremamine would be:

1) grind to powder (if possible), cold water soak 1-3 weeks (optional freeze/thaw cycle)

2) powder, soak ethanol 24-72 hours, non-heat evaporate most ethanol, add water or dry

3) grind fresh (still moist) bark, cold water soak

4) scrape sappy parts of live bark, soak in cold pure, river or rain water (partial replication of some reported old Jeruma technique..be great if we knew the songs too!)

of course, different amounts or durations of heat, or PH manipulation, could result in different kinds of breakdown by-products..maybe, for instance, with just a little low heat you would have something slightly devolved from yuremamine (but still possible maoi) plus some dmt..

One idea would be to extract DMT or synth it in a lab, and then add on the extra rings or compounds. The resulting molecule would be legal

interesting idea Hyperspace Fool, i'm no lab chemist, but complex indoles would seem to naturally lend themselves to easy (if not understood) manipulation..

..oh, the hours of fun for the seeker

.

 

[Hyperdimensional Cuttlefish]

If some of the 'undiscovered' psychoactives are heat and pH sensitive, then option 3-4 would make the most sense? Assuming they aren't a byproduct of 'curing' after processing raw bark per se. E.g. the plant material is subjected to significant drying and heating dring shredding and/or powdering (moreso), and shipping.

I dunno. I have a large dose (40g) of MRHB sitting in the fridge for a few weeks, will report on comparative experience to vaped and standard acid wash MRHB aya in the next few weeks yet.

 

[nen888]

thanks Hyperdimensional Cuttlefish..

Hyperspace Fool wrote

Yuremamine extraction and cold water infusions of Jurema have intrigued many of us since we first became aware of the possibilities.

yeah, i'm interested how much modern folklore is out there about cold-water mimosa brews..?
..some people i know say cold-water P. viridis teas have a different quality...

 

[nen888]

..found a really interesting paper on Psychotridine, which may also relate to yuremamine (thanks wira)
N. K. Hart et al. "Psychotridine, a C55,H62,N10 Alkaloid from Psychotria beccarioides" (Rubiaceae)
Aust. J. Chem., 1974, 27, 639-46
..i have attatched it below..

the paper determined the identity and structure of the major alkaloid of Psychotria beccarioides, found in lowland rainforest in New Guinea..the alkaloid hodgkinsine had previously been isolated from Hodgkinsonia frutescens (Rubiaceae), they played around with the new psychotria alkaloid:

.~
Whereas hodgkinsine is composed of three distinct N-methyltryptamine units, it appeared
from molecular weight determinations by vapour pressure osmometry that the new base from
P. beccarioides has five such units.

It is clear from the mass spectrum of psychotridine that the molecule breaks into two
principal fragments which contain respectively two and three N-methyl-tryptamine units.

It has been shown, moreover, that the tri-indolenine base from hodgkinsine reacts with
sodium borohydride in ethanol apparently to give a tetrahydro derivative which then fragments to give N,N, -dimethyltryptamine.

..so this would seem to indicate that it is possible DMT is derived (at least in part) from yuremamine in MHRB..could there be breakdown conditions in which MAOIs and the tryptamine are present?
anyhow, dimethyltryptamine from hodgkinsine sounds promising..
.

 

[endlessness]

Very interesting Nen! That molecular structure with the 5 indoles looks amazing!

Though notice that sodium borohydride is a strong reducing agent, I dont think any chemical naturally found in plants could emulate such reduction reaction, but given my lack of expertise, I could certainly be wrong though. Maybe different enzymatic processes could be involved.

Now question, what is the toxicity/pharmacology of these compounds?

 

[nen888]

..i'm looking into it, but they don't seem to have acute toxicity..

hodgkinsine: 100-500mg/kg orally in mice caused "CNS depression, hypersensitivity to external stimuli. and vasodilation." lower doses caused mild sedation & "loss of balance" [CSIRO 1990]
psychotridine: 35mg/kg I.P. in mice caused "CNS depression of a long duration, dsypnea, ataxia and deep respiration." [CSIRO 1990]
..these are really big doses..there were no deaths..

as for yuremamine, i would also assume fairly low toxicity based on ethnobotanic data etc..
.

 

[SKA]

Very interresting Topic.
Hyperdimensional Cuttlefish is right, Drying is likely to degrade sensitive molecules.
Shredding creates quite a lot of heat too. THe less friction the better.

Perhaps it would be better to dip freshly cut bark in water and let them soak up water.
Then put them in the Freezer for some hours untill they're frozen stiff. Then you could
wrap them in a towel and beat them to a powdery pulp with a rubber head-hammer.
This way the temperature stays much lower while the material is crushed.

If you could get some liquid Nitrogen, you could just freeze chunks of bark solid in a
matter of seconds. This way they should get really brittle and be easily pulverised.

Then you could try soaking that pulp in cold water. Be sure to use cold, destilled water.
If instead, you soak the pulp in Cold Alcohol you could perhaps filter our the pulp and
put the solution in the freezer for +/- 1 hour to see if anything will precipitate out.
[Could other solvents dissolve Yuremamine too, like Di-ethyl Ether, Naftha or Acetone?]


I read here and there in this Topic that Heat & Bases easily degrade Yuremamine.
Is Yuremamine equally sensitive to Acids?

 

[nen888]

..thanks for the interest SKA,
well, it seems Dozuki has gone a long way to characterizing what the breakdown products of Yuremamine would be in this thread..
& in the case of Hodgkinsine (see above), would certain conditions lead to it first decomposing into NMT and other compounds..?

..the single reported finding of a Spermidine alkaloid in the australian A. myrtifolia
has made me become interested in this class of alkaloids which are also known
from various micro-organisms and rat-liver.

The first example of this new alkaloid group was the spermidine alkaloid lunarine (7), isolated by E. I-lairs' in the year 1908 from Lunaria biennis
Moench (Cruciferaceae). Its correct structural formula was first established in 1965 by G. A. Sim and J. A. D. Jeffreyes ... The next alkaloid of this group to be isolated was palustrine from marsh horse tail Equisetum palustre L. (Equisetaceae)by Glet et al...potassium hydroxide fusion of the alkaloid gave the basic amine, spermidine, as well as some lower amines.

The main interest for us lies in the plant putrescine derivatives containing an amide group, formed by combination of the base
with p-hydroxy cinnamic acid or derivatives of it.

MACROCYCLIC SPERMID1NE AND SPERMINE ALKALOIDS
M. M. Bawia, K. Bernauerc, P. Van Den Broek, D. Groger, A. Guggisberg, S. Johne, I. Kompis, F. Schneinder, H.-J. Veith, M. Hesse and H. Sschmid.


i'm hoping wira will be able to post the proposed structures of Acacine (the A. myrtifolia spermidine alkaloid)
by Nicholls [1983]..i believe it was not conclusively structurally determined..

..i'm wondering if the chemically-inclined out there can tell me anything about these Spermidine of compounds, particularly the amide aspect..what would, for instance,
Lunarine, pictured below, potentially break down into..?

 

[Spiceman]

..thank you for your responses Simon Jester, endlessness, & Hyperspace Fool..

yes, i'm also hoping some more knowledgeable of chemistry can offer some ideas..
i'm also interested in what the possible degradation products could be..

..endlessness, thanks for clearing up the reference

regarding if DMT could originate from a more complex form, isnt it more reasonable that it starts at simple and goes more complex? Tryptophan->Tryptamine->DMT (and then -> whatever else -> yuremamine ?) Maybe our experts should give their input

yeah its possible it gets complex think of the simple shroom

Tryptophan->Tryptamine->DMT (and then -> whatever else -> like 4-ho dmt.. aka psylocibin or psylocin... thats proof they get more complex in nature.. its no doubt they also start somewhere around there and work backwards as well .

godspeed all.

 

[nen888]

..don't know where wira vanished to with the Acacine proposed struture (the spermadine alkaloid from A. myrtifolia) ..can't you access a scanner..? ..in the meantime, i've bumped this thread because it still interests me..
also, as DMT is slightly polymorphic (has two arrangements with different melting points), the complexity of things like the NMT-hyper-matrix described above could be twofold..
..like, inside a plant in solution..where does one 'molecule' begin and another end..?

 

[nen888]

...i've already attactched the Psychotria beccaroides paper earlier..i'm really interested what kind of crystalline structure such things would have..
a quote fragment summary of the paper is : (see image below for brackets (#))

.~Whereas hodgkinsine (1) is composed of three distinct Nb-methyltryptamine units, it appeared from molecular weight determinations by vapour pressure osmometry that the new base from P. beccarioides has five such units. (4) (Psychotridine)..
Two other alkaloids more complex than hodgkinsine have been reported recently to occur in H.frute~cens.~These alkaloids are quadrigemine A (2) and quadrigemine B (3), both of which have structures made up from four linked Nb-methyltryptamine…
~Hodgkinsine forms an Nb,Nbl,Nb"-trimethiodainde, in alkaline solution the trimethiodide is converted very smoothly into a tri-indolenine base..
It has been shown,3 moreover, that the tri-indolenine base from hodgkinsine reacts with sodium borohydride in ethanol apparently to give a tetrahydro derivative which then fragments to give Nb,Nb-dimethyltryptamine and an indolyl- indoline

Dried leaves of P,beccarioides (4.5 kg) were milled and extracted by continuous percolation with ethanol at 40". The crude alkaloids (9.6 g), isolated by the method previously de~cribed,s~till contained much non-alkaloidal material. Extraction with benzene gave a large amount of insoluble, apparently non-basic, material and the benzene-soluble portion (5.1 g) was chroma'tographed on neutral alumina. A series of fractions eluted by benzene were combined and crystallized to give psychotridine (2.1 g). Later fractions eluted by benzene and mixtures of benzene and chloroform afforded only small amounts of psychotridine.
The mother liquors from crystallization of psychotridine were examined by thin-layer chromato- graphy.

hodgkinsine (1); quadrigemine A (2); quadrigemine B (3) & Psychotridine (4)

 

[nen888]

..yeah sorry, chemical nerd land here, but for follow-through'sake - the proposed structure of Acacine, the spermidine alkaloid mentioned earlier..[Nicholls 1983 PHD thesis] from acacia..

..can anyone who's a chem-wiz tell me anything they might note about it? (or possible breakdown components) ?
i suppose i can email some overworked ones..

 

[The Meddling Monk]

Looks like a carbohydrate mixed with an amine. But I'm no chemist. Very interesting new class of alkaloid, thank you Nen for taking this lead.