Data on 5-AcO-DMT / O-Acetyl-Bufotenin

[Brennendes Wasser]

There is practically no information about 5-AcO-DMT on the Internet (not to be confused with 4-AcO-DMT).

Here is some maybe helpful stuff:​

Solubility:

boiling n-Hexane (69 °C)
5,0 g in 1 L
500 mg in 100 ml

n-Hexane in the freezer (-20 °C)
1,3 g in 1 L
130 mg in 100 ml

besides for sure super soluble in all kind of solvents like DCM, Ethanol, Acetone, EtOAc, Xylene, ...​

Phase Transitions:
Measured with IR Thermometer on a hot plate (give it +- 5 %)

Melting Point
83 - 88 °C

First fumes starting
190 °C

No fumes arising anymore
240 °C​

IR-Spectrum (measured in attenuated total reflection method (ATR)

UV-Vis spectrum (concentration < 0,01 wt-% in Acetonitril)

Bioassay:

no effect lol​

long story:

20 mg 5-AcO-DMT were vaporized over the course of 10 min.
The vapor taste is very smooth and not yukky like 5-OH-DMT. Also it does not turn black upon heating and vaporizes without any residue - just like pure DMT. In contrast this is not the case for 5-OH-DMT. It quickly turns black above 170 °C and only 50 % will vaporize, while the other 50 % will form a black burned layer on the surface, no matter how soft and gently you are heating it.
Seems like the 5-OH is the source of evil regarding the properties of 5-OH-DMT aka. Bufotenine which makes it hard to crystalize and also generates an unconvenient vaporization profile. Therefore the 5-AcO seems to make the molecule much easier to handle in any way.

Nevertheless no effect was felt. :roll:

Vaporization overcomes first-pass-effect by the liver, maybe this is a reason. 5-AcO-DMT should be a prodrug of 5-OH-DMT. De-Acetylation should be fast in the body, but no idea where it takes place - maybe that step is skipped when inhaling vapors. Nevertheless that would mean the prodrug is totally inactive. Compared to Psilocin, its prodrug 4-AcO-DMT is reported to be instantly active when inhaled, suggesting it has an effect itself. Therefore it would be strange if thats not the case for 5-AcO-DMT. Only solution would be: What you see in the first picture is not 5-AcO-DMT, which is nearly impossible, but cant be proven by MS or NMR right now.
Still, it has a distinct Tryptamine / Alkaloid taste. Maybe I should spend some time comparing the IR to this one.

3257 is hard to see, but might be there
(2186 not in literature spectra)
1752 is there
(1698 not in literature spectra - Acetic Acid?)
1373 is there
1216 is there
1168 is there
948 is there

... seems like true 5-AcO-DMT. 2186 + 1698 might be any residual stuff, but their signals are quite strong and in contrast the purity should be super high.

 

[downwardsfromzero]

Great work, BW. I'm always impressed by your practical efforts.

Compared to Psilocin, its prodrug 4-AcO-DMT is reported to be instantly active when inhaled, suggesting it has an effect itself. Therefore it would be strange if thats not the case for 5-AcO-DMT. Only solution would be: What you see in the first picture is not 5-AcO-DMT, which is nearly impossible, but cant be proven by MS or NMR right now.

Maybe 5-AcO-DMT is inactive as a prodrug because of steric bulk and/or bad electron distribution? Then metabolism stops the 5-OH from getting to an active concentration in any of the important places, if that makes sense.

 

[Brennendes Wasser]

So it always bothered me too much that this (whatever it was) substance created in 2020 had no activity. It looked just like it worked perfectly: The product dissolved in Hexane, had a lower melting point, evaporated completely and was white. The last one is an important sign of Acetylation, because Acetyl is an electron withdrawing group and will stop the phenolic O of Bufotenin to increase electron density in the indol chromophor. This former '+ M Effect' is reduced, hence it will not cause the red-shift (shift of photochromic properties to longer wavelengths) and be white again. I could not do a sophisticated analysis, but FTIR showed also the typical Acetyl signals and all Acetic Acid smell was gone, so it must come from that compound.

Because Bufotenin cannot be smoked conveniently I now wanted to give it another try as 5-AcO-DMT should be just a masked Bufotenin which will conveniently vaporize and not decompose, as explained here. I dont even remember how the reaction what led to above product was conducted, but I guess it was rather freestyle , which means no catalyst and heated to the maximum. Now I tried a more refined method from literature which was proven to work for Psilocin (4-OH-DMT, Bufotenin is 5-OH-DMT), but that on the other hand gave absolutely no conversion. Therefore I took a look again into my old inactive sample from 2020. Therefore still no 5-AcO-DMT to be tested, but that finally solved the mystery above whatever compound above is.

The old sample gave off a lot of acetic acid smell during that years and turned brown again, which might hint that a back-reaction to Bufotenin took place. But anyways I analyzed it with 1H-NMR:

So here is the explanation for everything: Indeed the acetylation worked, which would possibly render the substance clear white, also reduce melting point and stop polymerization at high temperatures. That successfull and desired O-Acetylation can be seen at 1,92 ppm. Hooray, it indeed worked, Integral is just 2,43 and therefore only ~ 81 % of Bufotenin is still O-Acetylated. That explains the ongoing release of Acetic Acid.

But now here comes the interesting (and annoying) part. There is also the proof of N-Acetylation with a signal at 2,56 ppm. That's why the structure shown above is O-Acetyl,-N-Acetyl-Bufotenin. The integral is mixed with a R2CH2 group and actually too big, but anyways ... it shows that whatever conditions I used during that time were too harsh and also made that Pyrrol-N react.




Now why is it inactive?

Just speculation, but I'm pretty sure the electronic properties of the chromophor were drastically changed by reaction of the Amine to the N-Acetylated Amine = Amide. Why is that stoppind bioactivity for N-Acetylation and not for O-Acetylation?

The O can be regarded as a Sidechain of the pharmacologically active structure of the drug. The latter is also called Pharmacophore - this is the actual backbone / scaffold of a drug that will trigger it's activity at a certain protein. In pharmaceutical research it is important to first identify this elementary structure of a desired drug family and then construct all side chains around it in a way that a certain pharmacodynamik and pharmacokinetic is achieved. Because of that the O-Acetylation as a sidechain substitution is just changing minor properties that alternate the psychedelic experience, like a difference between DMT, 5-MeO-DMT, Psilocin, Bufotenin, ... But the Pyrrol-N is propably really important for in-vivo recognition of the drug. Amines exhibit strong nucleophile interactions and are therefore an important 'biochemical tool' to interact with electrophile domains of proteins and enzymes. Therefore if their electronic properties change too much, like creating a non-nucleophile Amide from an nucleophile Amin, then this interaction is blocked. Same is observed with DMT-N-Oxide compared to DMT. In my test 100 mg pure DMT-N-Oxide ingested was completely inactive, probably because that Dimethyl-Amin of the sidechain is also important in exatly the same way.

This comes at no wonder, as the Tryptamin motive is present throughout a lot of endogeneous substances, as they all are derived from Tryptophane. If the backbone of that molecule changes too much, it is probably impossible to be recognized by a lot of receptors. A sign from real life is that you will find no designer drugs that are N-Acetylated. The only exception that comes to my mind are those (not anymore) "legal LSD-variants" 1P-LSD, V-LSD, ... which carry the Tryptamine-Motif, but are N-Acetylated (to evade the law). But these molecules are so big that probably other atoms are crucial for in-vivo recognition, therefore here it does not matter much I guess ...

So that finally solves the mystery about that inactive substance, still it means all trials of getting 5-AcO-DMT were not successfull as either no Acetylation or double Acetylation happened. I could do a row of experiments at like 20 different temperatures and see where I have the best parameters for Mono-Acetylation, but I neither have the time nor the Bufotenin for all that :thumb_dow