tryptophan/H202/HCL?

[entheogenic-gnosis]

In Michael v. Smith's "psychedelic chemistry", after a tryptophan decarboxylation work up, it is claimed that oxidation of tryptophan using hydrogen peroxide, then reaction HCL produces a psychedelic compound...

It also claims the initial reference did not leave a work up or further explanation.

I can't locate the original work up, and have higher priority research to conduct, but this claim caught my attention, well, at least enough to make a quick post before it slipped my mind.

M.V. Smith ; psychedelic chemistry

Tryptamine from tryptophan JCS 3993 (1965)


tryptophan, if oxidized by H202, and cyclized by HCL gives a psychedelic compound

-eg

 

[entheogenic-gnosis]

Tryptamine from Tryptophan JCS 3993(1965)

10 g tryptophan in 500 ml diphenyl ether; reflux one hour under N2; cool and extract with 3x40 ml 2N HCl. Wash extract with ether, basify with 6N NaOH and extract with 5X50 ml ether. Wash extract with water, NaCl; dry and evaporate in vacuum and recrystallize-benzene to get tryptamine which can be alkylated to dialkyltryptamine as described previously.(Tryptophan, if oxidized by H2O2 and cyclised with HCl, gives a psychedelic compound.) Much interest has been generated by the mention of tryptophan oxidation to a psychedelic compound, but the original reference gives no details of the method.

Psychedelic Chemistry - Magic Mushrooms and Other Indole Trips

I found a transcription online (above), thought it should be posted here as well.

-eg

 

[entheogenic-gnosis]

Any ideas on where to find this "original reference" which was mentioned?

Or any ideas on the source of this information? (Other than smiths psychedelic chemistry?)

-eg

 

[entheogenic-gnosis]

What's the deal here?

Oxidation of tryptamine to 3-Indolylacetaldehyde with H202 then a modified Pictet–Spengler reaction of 3-Indolylacetaldehyde using HCL as a Brønsted acid, to give some beta-carboline?

If I'm way off let me know...

I generally don't have time to confirm or explore random claims, and this has been low priority, but ever since I saw that line of text I've been thinking, what was the deal here?

-eg

 

[entheogenic-gnosis]

Oh shit, tryptophan oxidation! Not tryptamine! I misread, my fault!

-eg

 

[entheogenic-gnosis]

The oxidation rate of Trp and the formation of 16 possible degradation compounds were examined using RP-HPLC and UV, fluorescence, and photodiode array detection. The rate of Trp degradation increased from lysozyme to short-chain peptides to unbound Trp
Oxidation of Free Tryptophan and Tryptophan Residues in Peptides and Proteins - PubMed

Oxindolylalanine (Oia), 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid (PIC), N-formylkynurenine (NFK), dioxindolylalanine (DiOia), kynurenine (Kyn), and 5-hydroxytryptophan (5-OH-Trp) were identified in this order of quantity as degradation compounds, showing the Trp pyrrole moiety to be most susceptible to oxidation

So a cyclized version of one of these compounds which was cyclized with HCL?

Abstract
The oxidation of free tryptophan (Trp) and Trp residues in peptides and proteins by hydrogen peroxide as oxidative agent has been used to evaluate Trp losses and the pattern of degradation products formed. Besides free Trp, four Trp-containing peptides and lysozyme were used as substrates in the aqueous model system. The oxidation rate of Trp and the formation of 16 possible degradation compounds were examined using RP-HPLC and UV, fluorescence, and photodiode array detection. The rate of Trp degradation increased from lysozyme to short-chain peptides to unbound Trp. Only approximately 20% of the total Trp loss could be elucidated by the determined Trp degradation compounds. Oxindolylalanine (Oia), 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid (PIC), N-formylkynurenine (NFK), dioxindolylalanine (DiOia), kynurenine (Kyn), and 5-hydroxytryptophan (5-OH-Trp) were identified in this order of quantity as degradation compounds, showing the Trp pyrrole moiety to be most susceptible to oxidation. As short peptides such as H-Ala-Trp-Ala-OH were completely hydrolyzed with immobilized Pronase E, Oia and NFK could be identified as main degradation compounds, as could minor amounts of Kyn, DiOia, PIC, and 5-OH-Trp. Acid (6 M HCl), alkaline (4.2 M NaOH), and enzymatic hydrolyses were compared for the determination of Trp degradation compounds in lysozyme. Kyn, Oia, and DiOia could be detected in the hydrogen peroxide treated protein.

Am I getting closer?



-eg

 

[entheogenic-gnosis]

More information on the products resulting from tryptophan oxidation with h2o2

New oxidation products and free radicals derived from tryptophan (Trp) oxidation under Fenton reaction conditions were identified using mass spectrometry. After the oxidation of tryptophan using hydrogen peroxide and iron (II) system (Fenton reaction), mono- and dihydoxy tryptophans and N-formylkynurenine were identified using electrospray mass spectrometry (ES-MS) and ES-MS/MS. Besides these products, new products resulting from the reaction of tryptophan and oxidized tryptophan and 3-methyl indole derivatives were also identified. The 3-methyl indole derivatives resulted, most probably, from the oxidation process and not from in-source processes. A dimer formed by cross-linking between two Trp radicals (Trp-Trp), similar to the previously described tyrosine dimer was observed, as well as the corresponding monohydroxy-dimer (Trp-Trp-OH). Tandem mass spectrometry was used to identify the structures of these new oxidation products. Free radicals derived from tryptophan oxidation under Fenton reaction were detected using as spin trap the DMPO. The free radical species originated during the oxidation reaction formed stable adducts with the spin trap, and these adducts were identified by ES-MS. New adducts of oxidized tryptophan radicals, namely monohydroxy-tryptophan and dihydroxy-Trp dimer radicals, with one and two DMPO spin trap molecules where identified. Tandem mass spectrometry was used to confirm the proposed structure of the observed adducts

http://www.sciencedirect.com/science/article/pii/S1044030503001272

-eg

 

[entheogenic-gnosis]

Where did this original reference come from?

I guess that's my final question, unless any chemists out there who are a bit more learned than myself care to weigh in on this one...

-eg

 

[entheogenic-gnosis]

So I was thinking about novel cyclization products of tryptamine compounds, and I remembered a passage I had read in TIHKAL quite some time ago...

(This passage appears in my printed copy of TIHKAL, however erowid's online version of TIHKAL left this last paragraph out, I'm not sure why, it was probably a mistake. )

A fascinating cyclization product of this "nor-compound" [5-meo-NMT] is a cyclic dehydrogenation product where there is a direct coupling of the tryptamine nitrogen to the 4 position of the indole ring. This tricyclic material, O-methyl-nor-dehydrobufotenine proved to be of comparable activity to DMT in rat studies, but has not apparently been studied in man

Shulgins compound has the amine nitrogen connecting directly to position 4 of the indole ring, these next compounds are cyclized by the alpha carbon of the ethyl side chain connecting to an additional carbon which connects to position 4.

(First picture is O-methyl-nor-dehydrobufotenine, second picture is RU-28306 )

RU-28306 is a tricyclic tryptamine, only there is another carbon cyclizing the alpha carbon in the ethyl side chain to a carbon on position 4...This compound has always fascinated me, it's both a simplified version of LSD or a cyclized version of DMT depending on how you look at it.

1,3,4,5-tetrahydro-6-methoxy-N,N-dipropyl-benz[cd]indol-4-amine (Bay R 1531) is another tricyclic tryptamine, only this time the alpha carbon of the ethyl side chain of DPT has been cyclized to.an additional carbon connecting to position 4...

Could the compound mentioned involving an oxidation product if tryptophan which was cyclized with HCL be similar to these compounds?

-eg

 

[entheogenic-gnosis]

I've searched for further reference, but came up empty handed.

I would have just let this one go, however there's a level of plausibility here that's kept me in research.

I was hoping there would be others who know chemistry a little better than myself who could weigh in on this one, but it looks like I'm on my own on this topic.

Regardless, a potential psychedelic claim always catches my attention, and honestly, it looks like there may be something here.

-eg

 

[downwardsfromzero]

All I can suggest is something like the nordehydrobufotenine without the methyls and maybe the carboxy group intact. Otherwise perhaps something akin to adrenochrome? Anything involving dimerisation or beyond and we start to get decidedly complicated. That really is a most apocryphal tidbit from MVS!

Why not just oxidise some Trp and see what comes out? Method seems simple enough, conditions and workup are of course the trick.

(I think this just about escapes being s*nth talk )

 

[entheogenic-gnosis]

The only discussion I could uncover on the topic was left wondering as well...

Most seem.to think that it was describing a modified Pictet–Spengler reaction using HCL as a Brønsted acid to give some beta-carboline, however I don't think this is at all the case

Oxidative modification of tryptophan to kynurenine (KYN) and N-formyl kynurenine (NFK) was also looked into, but has no relation to the topic at hand.

This has been driving me crazy, where did this reference come from? I can't locate the source of this little piece of information, aside from "psychedelic chemistry" I can't find a single reference to this...

-eg

 

[downwardsfromzero]

Hmmm... one of them kynurenine bits may then participate in a Pictet-Spengler with remaining unreacted Trp. That would make a curious 1-substituted betacarboline.

Not all chemistry ends up in journals, I suppose. I once made some copper hydride in my bedroom, using aluminium foil as the reductant! Only worked out what it was about 8 years later, shame it decomposed in half an hour

 

[downwardsfromzero]

Now, this oxidised tryptophan mullarkey would be one for Benzyme's new LCMS!