Biosynthesis of Psilocybin from 4-HO-L-Tryptophan

[Jabberwocky]

First of all this is not a synthesis discussion. It is a biosynthesis discussion and an important one at that. A simple one-pot biosynthesis of one of the staple psychedelics.

Janis Fricke, Felix Blei, and Dirk Hoffmeister of Friedrich Schiller University Jena have identified and characterized to the greatest extent so far the four enzymes that the mushrooms use to make psilocybin. The team then developed the first enzymatic synthesis of the compound, setting the stage for its possible commercial production (Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201705489).

Link to scholarly article: http://onlinelibrary.wiley.com/doi/10.1002/anie.201705489/abstract

Read a non-technical description of the finding from C&EP: http://cen.acs.org/articles/95/web/2017/08/Magic-mushroomenzyme-mystery-solved.html?utm_source=Newsletter&utm_medium=Newsletter&utm_campaign=CEN

 

[Solipsis]

Notice the word "production" there? Or "one-pot" for that matter? Biosynthesis is synthesis, maybe an exception is when it is so advanced that it's harmless to discuss since it would be so unfeasible for a clandestine operation. I do admit it's right on the line there... and the rules are fuzzy:

Discussion of mushroom cultivation is allowed here, but handling materials containing psilocybe alkaloids is illegal in the US whereas in my country they outlawed cultivation of shrooms but not sclerotia (magic truffles).. As nothing involving the aid of manufacturing drugs via cultivation / bio or not bio synthetic routes is ultimately wanted on Bluelight, you can consider discussion of shroom cultivation for personal use a condonement policy probably... discussion of cannabis cultivation seems much more controversial for here (although I don't visit CD) even though it is being legalized in places around the world.

A little more on the right side of the line would be liquid cultures of Psilocybes: this is still considered part of mushroom cultivation.

As enzymatic synthesis isn't really feasible without a professional lab afaik, this seems harmless to talk about, but ultimately not because Bluelight would care about enzymes being used rather than more typical reagents. Similarly in various places in the world, the point where you break the law is when you start processing plant materials rather than leaving them as is. (whatever that may mean - still it is why hash oil is considered more seriously illegal here). For the average person it would more reasonable to use the naturally produced enzymes in some way or another.

 

[Jabberwocky]

Thanks for letting this through. I think this is well within the spirit of the law. When the transgenic morphine-producing bacteria news story came out Bluelight was lit up with discussions about it. It takes an experienced biochemist with a well equipped lab to replicate this. Meanwhile the societal impact of this could be big. Cheap psilocybin by the barrel. Bluelight gotta' stay on top of this. I dare say it is our duty.

 

[Hodor]

Cheap psilocybin by the barrel.

The total synthesis of psilocybin is already cheap af; Hofmann did it in 1958. It's just illegal. If it were legal, you could just buy kilos of it from chinese suppliers, like you currently can with 4-AcO-DMT.

Enzymatic synthesis is much more interesting for compounds with complex polycyclic structures with multiple stereocenters like morphine or salvinorin.

 

[Scrofula]

Don't forget the FBI or Postal Inspectors or whoever aren't good at distinguishing fun home chemistry projects from illicit manufacture. They like to check it out only after SWAT has knocked your house down and shot your dog.

Biggest problem for enzymatic synth is cloning those enzymes. It doesn't look like Popaver is sequenced, and I'm sure Psilocybe isn't. If it's rare in the world, you couldn't even search by homology. If it's a lot of steps, that's a lot of enzymes, and a lot of yeast strains, and a shit ton of work. You could have a toxic intermediate or an enzyme that crashes out or needs some accessories to activate it.

The equivalent in vertebrates is tryptophan 4-hydroxylase, which requires a TBH cofactor and something to phosphorylate it. That was probably half a dissertation, and you're starting from scratch with the mushrooms.

But once you get by that hurdle . . . only a freezer, flasks, a shaker and a lot of sugar (and antibiotics and other nutrients, but those are cheap).

 

[Xorkoth]

The total synthesis of psilocybin is already cheap af; Hofmann did it in 1958. It's just illegal. If it were legal, you could just buy kilos of it from chinese suppliers, like you currently can with 4-AcO-DMT.

Synthetic 4-HO-DMT was briefly made available back in 2006, I got to try some. They produce other things that are illegal too clandestinely (LSD for fuck's sake, which is much more difficult of course). If it's really easy to make, I wonder why no one is doing it? I'd love to get my hands on some more, I found it significantly different from 4-AcO-DMT and also different from mushrooms, though much closer to mushrooms of course.

 

[Bigazznugz]

I don't think many people make synthetic 4 ho dmt because we'll you can grow shrooms for litterally just spore price and the cost of substrate.
You know how a lot of people are they always think (shrooms) are better because they come from the Earth not from a pot of a yeast strain that is probably not even available. In the future this could could be big thing but for now I would think shrooms are King if you wanna trip on 4ho dmt.

 

[Scrofula]

I'm not a real chemist, but I think sticking a hydroxyl at the 4 position, starting with nothing, is pretty damn difficult.

So yeah, spores can be sent through the mail, a bit easier.

 

[Hodor]

Synthetic 4-HO-DMT was briefly made available back in 2006, I got to try some. They produce other things that are illegal too clandestinely (LSD for fuck's sake, which is much more difficult of course). If it's really easy to make, I wonder why no one is doing it? I'd love to get my hands on some more, I found it significantly different from 4-AcO-DMT and also different from mushrooms, though much closer to mushrooms of course.

LSD, while illegal, is also extremely potent (1 gram of LSD equals approximately half a pound of Psilocin), which also makes it very easy to distribute.
4-AcO-DMT is legal in most of the world. Psilocybin is illegal, but it can be produced using mushrooms that will literally grow on shit.

Psilocin, on the other hand, is Schedule 1 under the UN Convention on Psychotropic Substances, and explicitly banned under national law in most industrialized countries. Yeah, its effects may be slightly different from 4-AcO or Psilocybin, but probably not enough for your average psychonaut to tell them apart in a blind test (compare that to 2C-B, which is also quite illegal and not super-potent, but also fairly unique in its effects). Furthermore, Psilocin is significantly less stable than its esters.

tl/dr: It's not that 4-HO-DMT is hard to make, it's just that it's not worth the risk as long as 4-AcO is legal and shrooms exist.

 

[Xorkoth]

Yeah good points there.