Sciencemadness Discussion Board

Dimethylation of Tryptamine with amine N-methyltransferase

TheEnlightenedScientist - 23-2-2015 at 09:26

Hello members of Science Madness!

I am just starting to educate my self about organic chemistry and the mechanisms that are involved. For some time i have been reading about the indole family and the different tryptamines that are present in nature.

I noticed that there are already different routes from Tryptophan to Tryptamine. Where tryptamine is a very interesting compound but often very expensive. My question is if it is possible to Dimethylate Tryptamine using an amine N-methyltransferase. S-adenosyl-L-methionine or (SAM) is often used in this progress doing the following procedure:

S-adenosyl-L-methionine + an amine <=> S-adenosyl-L-homocysteine + a methylated amine

Since Tryptamine can be made fairly OTC and cheap by the decarboxylation of Tryptophan and S-Adenosyl-L-methionine(SAMe) (S-Adenosyl-L-MethionineDisulfate p-toluenesulfonate) is easily available as a food supplement. This can be a pretty good route to yield N,N-dimethyltryptamine.

Can anybody tell me if this way is plausible?

-TheEnlightenedScientist

Chemosynthesis - 23-2-2015 at 09:50

I'm not really sure you posted this here, as it's not really organic chemistry, nor is this forum a drug forum, but if you have to ask how to make drugs, I doubt you have the requisite sources of tryptamine-N-methyltransferase (which you didn't mention), or could optimize reactor design given the turnover of whatever homolog/isoform you choose.

mayko - 23-2-2015 at 16:17

Tryptamine is dimethylated in vivo by an indoleethylamine-N-methyl transferase. I'm rather skeptical that you could get it working at all in vitro, let alone whether this would be an effective means of getting the target molecule in ... useful quantities.

If molecular biology is your interest, engineering E. coli/arabidopsis to overexpress INMT and growing them on tryptophan/SAM-rich feedstock would be a potentially productive, though likely challenging and felonious, DIY project.

A few papers you might find interesting:

Axelrod, J. (1962). The enzymatic N-methylation of serotonin and other amines. The Journal of Pharmacology and Experimental Therapeutics, 138, 28–33.

Baxter, C., & Michael Slaytor. (EDIT: 1972). Biosynthesis and Turnover of N,N Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine in Phalaris Tuberosa. Phytochemistry, 11(1966), 2767–2773.

Mack, J., & Slaytor, M. (1979). Indolethylamine N-methyl transferases of Phalaris Tuberosa, purificantion and properties. Phytochemistry, 18, 1921–1925.






[Edited on 24-2-2015 by mayko]

Chemosynthesis - 24-2-2015 at 04:38

Quote: Originally posted by mayko  
Tryptamine is dimethylated in vivo by an indoleethylamine-N-methyl transferase.
same enzyme. It has at least six names. I wish people could standardize them because sometimes it feels like half my job is finding them all.

mayko - 15-8-2017 at 10:31

The biosynthetic pathway in Psilocybes has been unraveled; might be of interest. In particular, they found that the methylating enzyme is unrelated to the mammalian INMT.


Quote:

Psilocybin is the psychotropic tryptamine-derived natural product of Psilocybe carpophores, the so-called “magic mushrooms”. Although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure. We characterized four psilocybin biosynthesis enzymes. These include i) PsiD which represents a new class of fungal L-tryptophan decarboxylases, ii) PsiK, that catalyzes the phosphotransfer step, iii) the methyl transferase PsiM, catalyzing iterative N-methyltransfer as terminal biosynthetic step, and iv) PsiH, a monooxygenase. In a combined PsiD/PsiK/PsiM reaction, psilocybin was synthesized enzymatically in a step- economic route from 4-hydroxy-L-tryptophan. Given the renewed pharmaceutical interest in psilocybin, our results may lay the foundation for its biotechnological production.


Fricke, J., Blei, F., & Hoffmeister, D. (2017). Enzymatic Synthesis Of Psilocybin. Angewandte Chemie - International Edition, eingereich. http://doi.org/10.1002/anie.201705489

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zed - 15-8-2017 at 18:52

Well, some of those pesky little mushrooms that make Psilocybin, are native to my locale.

So, hereabouts, folks usually let the natural world do the work, and they either pick mushrooms wild, or they grow 'em at home in jars.

Now, DMT and some other Indole alkaloids, those materials are less easily acquired, and there is a lot of scientific interest in them. Thanks for the reference.