psilocin-O-sulfates?

[GC_MS]

Browsing some antique patents, I found something potentially interesting: the synthesis of 4-hydroxy-N,N-dimethyltryptamine-O-sulfates. I have some questions, and I hope somebody can answer them. I will commence by translating the patent.

Patent CH373382

- Verfahren zur Herstellung des bisher unbekannten 4-Hydroxy-N,N-dimethyltryptamin-O-sulfates. Dr Albert Hofmann und Dr Franz Troxler, Bottmingen, sind als Erfinder genammt worden. Sandoz AG, Basel. Zusatzpatent zum Hauptpatent

Patent CH371116

.

The synthesis of 4-hydroxy-N,N-dimethyltryptamine-O-sulfates, a former unknown compound.

We found that 4-hydroxy-N,N-dimethyltryptamine-O-sulfate (psilocine-O-sulfate, POSO3) can be obtained if psilocine (P) is reacted as an alkaline salt in an inert organic solvent with chlorosulfonic acid.

Procedure: A solution of 58 mg Na in 30 mL absolute EtOH is charged with 510 mg P (N2 atmosphere). After 15 minutes, the solvent is evaporated and the residue is stored in vacuo for another hour (very low vacuum necessary) at 70°C. Subsequently, 20 mL 1,2-dimethoxyethane and 305 mg chlorosulfonic acid are added. The reaction mixture is damped in after one hour and the residue chromatographed with a 50x mixture of cellulose powder and water-saturated n-BuOH. When the fractions are damped in, POSO3 will crystallize. Crystallization from MeOH yields needles, mp 251-252.
Keller spot test: "koenigsblau"
Van Urk spot test: "dunkelblauviolett"

So far the short patent. Now, my question(s) and why it might be interesting. Psilocine and its phosphate ester psylocibine are both scheduled substances in most countries. In a handful of regions, magic mushrooms containing the substances are tolerated.
It is known that psylocibine is metabolized to psilocine in the human body, which gives rise to the belief that psilocine is the actual active component of magic mushrooms. However, does the same happen with POSO3? Will the sulfate metabolize in the human body to psilocine as well? If yes, then we might have a nice legal alternative. You see, many countries list psilocine, psylocibine and various species of magic mushrooms as scheduled substances, but not POSO3. You could synthesize POSO3 and sell it on the hallucinogenic market as such, without doing anything illegal (depends on the laws of your country. The US Analogue Act...). And the effects will be similar. So, anyone who can answer the question?

[yellium]

Nice idea. But what if the local governments emergency schedule your psilocibine sulfate? Or, even better, hire a chemist to schedule all possible abusable psychoactive compounds you could think off, plus a few others?

[GC_MS]

Governments emergency-schedule all the time. If I say that POSO3 wouldn't be illegal, than I also know well enough that "the fun" might only last for half a year. And not all countries put a substance on schedule once it has been encountered on the black market. They usually do so if there have been several lethal accidents (for instance 4-MTA) or when it becomes evident that a new drug is becoming widespread. A good example is TMA-2, which is regulated in the US but not in Europe. This, however, does not mean that the drug has never been found overthere! They "don't see the need yet to schedule it right now".
And if POSO3 would work out nice, and if they would schedule it, well... then we find just another way, no?  

[yellium]

Gov'ments do not always wait for deaths. See the UK for example, where they scheduled almost everything listed in PiHKAL. And the EU might be relatively relaxed with some psychoactives, with others they've been faster than the US (2ct2/7 has been banned in sweden and .nl earlier than in the US).

[Kinetic]

See the UK for example, where they scheduled almost everything listed in PiHKAL

Make that everything . That includes TMA-2 and 2C-T-7, both class A since 19 fucking 86... In case any of our few UK bees read this, it's bad news on the sulfate ester too, as esters and ethers of any N-alkyl, ring hydroxy tryptamines are class A. Luckily, nobody has got round to scheduling fresh mushrooms yet over here .

Nice idea for the rest of the world though GC_MS, just be very careful when making legal analogues with controlled substance intermediates, especially if they're only one step from the final product.

I really don't see a problem with the hydrolysis in the body from the sulfate ester to the active psilocin, in the same way as the phosphate ester hydrolysis, but then I'm not a pharmacologist. I'm just using the general similarities between sulfuric and phosphoric acid to reach that conclusion; sulfate could be slightly easier to remove than phosphate, using it's lower pKa as a guide.

[GC_MS]

I asked the biochemical question to somebody with much more knowledgde on the topic, and she suspects the POSO3 to be mainly inactive.

The human body has several desulfatase enzymes, and as such has the capability to transform POSO3 to psilocine, the active compound. However, she said, sulfates are a way to eliminate substances via urine as well. The body transforms compounds to sulfates (Phase II metabolism), by which some of the most elementary properties change drastically. For instance, the pKa and its solubility. If POSO3 enters the blood, it remains higly soluble in the "aqueous phase" and will be unable to move through the lipophilic cell membranes. She also says that free phenolic functions are ideal for sulfatation, and that POSO3 might even be one of psilocine's metabolites. If POSO3 would have to generate an effect similar to psylocibine, the desulfatation has to occur in the stomach.

So far my short dreams   . If anyone has more ideas on the subject, please shoot   .

[Chimimanie]

What about psylocin-O-acetate? (4-Acetoxy-DMT)


Or maybe a benzyl on the O? (4-benzyloxy-DMT)

[GC_MS]

Could be possible. Also check out

Patent GB981192

for more information... [...] The compounds I above have interesting pharmacodynamic properties and/or are intermediate compounds for the production of pharmaceuticals. The exemplified compounds have been found to have interesting pharmacodynamic properties in animals, especially stimulation of the central sympathetic nerve system, which stimulation may be noticed by mydriasis, increased blood pressure, temperature increase and increased blood sugar as well as inhibition of intestinal activity; furthermore, some of them show serotonin antagonistic properties, favour spinal reflexes, have a slightly calming effect and counteract sedative and convulsive effect of reserpine. The compounds exemplified in Examples 1 and 5 have been found to have especially marked serotonin-antagonistic properties. [...]

[Lilienthal]

It's 'Psilocin' and 'Psilocybin'. UTFSE to find:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/psilocybin.html

,

Post 11807

(Lilienthal: "New tryptamine literature", Tryptamine Chemistry), and

Post 327507 (missing)

(alchemy_bee: "Effects Psilocin vs. Psilocybin", General Discourse)    

GC_MS: That's what I thought, but it's difficult (or nearly impossible) to predict the metabolism and elimination routes, especially in the case of this sterically hindered compound. The proof of the pudding is in the eating    (especially as the synthesis doesn't sound too complicated   ).

I vaguely remember that psilocin is metabolized by deamination and / or glucuronidation, but I might be wrong.

[Chimimanie]

Nichols' lab use O-acetyl psylocin in place of psylocybin

Look Nichols, David E.; Frescas, Stewart.  Improvements to the synthesis of psilocybin and a facile method for preparing the O-acetal prodrug of psilocin.   

Synthesis  (1999), (6), 935-938

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/psilocybin.html).

and Synthesis (1999), (11), 1999. for an erratum

as 4-Acetoxy-DET is active in man, the 4-acetoxy-psylocin should bee active too.


The 4-benzyloxy-5-MeO-DMT is active in animals, so it might be ok for 4-benzyloxy-DMT too.

At worst if it is inactive, just a little Na in ammonia to deprotect it and the bee hasn't wasted his time.  

Or maybe if legality is important for that bee, juss toss it and restart the synth with methylethyltryptamine, to synth some 4-OH-MET!

[yellium]

GC_MS: not everything you read in patents is true.

[GC_MS]

GC_MS: not everything you read in patents is true.

I know, but for some reason(s), "Albert Hofmann Sandoz Lab" sound abit more credible then "Rani Matahamandera Mumbai Technologies". I have encountered bogus patents in the past at more then just one occasion   .

Lili: tx for the clarification! I just keep on reading psilocin, psilocine, psylocibin, psilocybine, etc. everywhere in the published literature.

[yellium]

Yeah, but even reputable companies but disinformation in their patents. They don't want to give away all their secrets, y'know.

[GC_MS]

I know the feeling... I'm still trying to get something useful out of

Patent US4755613

...