Author Topic: LSD synthesis via peptide coupling (Read 362 times)

dream0n · « **on:** June 12, 2011, 05:18:28 AM »

On Rhodium there was one article about the synthesis of LSD via peptide coupling, I was wondering if anyone knows if this has actually been done or that it does not work.

Link:hxxp://erowid.org/archive/rhodium/chemistry/lsd.coupling.agents.html

The material on that page shows that over 90% yields are possible coming from Ergine.
A fairly simple and short procedure compared to most.
What I find is best about these synthesis, is that there are many possible coupling agents to use and that there is noted that using diethylamine substitutes can produce analogues, though most are not as desirous of products.
Source: hxxp://erowid.org/archive/rhodium/chemistry/lsd-buzz.html
All of these, and more might be substituted for diethylamine in the synthesis. Albeit for a loss in potency.
Ethylpropylamine, Morpholide, Methylpropylamine, Dipropylamine, Methylethylamine, Dimethylamine, Pyrrolidide
I suspect that these might not fall under the analogue act, but am not sure.

The Lone Stranger · « **Reply #1 on:** June 12, 2011, 09:04:38 AM »

A question . Where does the original information about the other chemicals that could be used to make an LSX come from ? Is it theoretical ? Have those LSXs been tested on humans ? Just because a synthesis would work theoreticly and practicly it doesnt mean that it would be a nice trip ?

xxxxx · « **Reply #2 on:** June 12, 2011, 12:42:53 PM »

This is one of the best experimental writeups I have come across regarding synthesis of LSD via peptide coupling. It is confirmed to have been tried and it works as Casey 'Freeblood' Hardison was later arrested by British police.

It looks like a really nice synthesis. If only the starting alkaloids were available! Hope it helps. Just be aware that there appears to be a few typographical errors in the text. Check everything if you are actually gonna give this ago!

akcom · « **Reply #3 on:** June 12, 2011, 01:32:16 PM »

The nice thing about this is PyBOP is relatively cheap, 5 grams for about $60 bucks, and readily available. Much nicer than POCl3

aniracetam · « **Reply #4 on:** June 12, 2011, 01:52:09 PM »

if anyone was interested where Casey got the idea, it was Nichols' paper on dimethylazetidine coupling

dream0n · « **Reply #5 on:** June 12, 2011, 08:34:28 PM »

Okay, about the effects of LSD analogues: "In human beings (2 volunteers) the effects of LSM were qualitatively similar to those of LSD but the dose required was at least 1/3 larger and the duration of action was shorter." hxxp://www.erowid.org/references/refs_view.php?ID=1563
That is concerning d-lysergic acid morpholide.

From Michael Valentine Smith Psychedelic Chemistry: LSD, "piperidine, diisopropylamine, ethylisopropylamine, ethylpropylamine, methylethylamine, methylisopropylamine, tetrahydrooxythiazine, tetrahydroisoxazine, dioxazole, 2-methylmorpholine, 2,5-dimethyl (or dimethoxy) pyrrolidine, cyclo-butyl-amine, cyclopentylamine" these chemicals are noted for being possible substitutes that would give a legal final product.
Link: hxxp://erowid.org/archive/rhodium/chemistry/psychedelicchemistry/chapter7.html

Hypothetically speaking, If someone were to preform any coupling synthesis of this sort, for a small scale using plant sources for Ergine is recommended, but for a larger scale production fungi would be preferred out of cost. In this example, A small scale is less than 10 grams of final product.

Also, it should be noted that the 'trips' from the analogues would be less in potency in most cases. Varying in duration.

The Lone Stranger · « **Reply #6 on:** June 12, 2011, 11:28:27 PM »

Cool that you sussed that out . Thanks . Not doubting you or what you found ........But --------->

Synical sam = me says ----->

"that would give a legal final product."

? Drug analog laws ? When was that M.V.Smith edition published ?

And erowid has loads of facts mixed with loads of shit in it = i dont believe anything there or anywhere else unless i can see real studys by real scientists who definately have used the real thing like the one you posted ......... but....... two people is a "bit" small ....... to have any statistical validity a test needs to be done with over a thousand people from what i`ve read . .... AND we all know how the same dose of LSD can do different things and seem to have a different strength at different times ....... plus how strong placebo can be < ----------- good example of erowid and web shit is ........ drinking piss to get a "trip" of fly agaric . Takeing a look at erowid for that was an eye opener . Last time i looked there was only one claim of anyone actualy doing it and haveing sucsess and the poster was obviously ......... a wanker .......... ....... So whos realy done it ? .............. I´ve been to big international conferences where people ....... "experts"....... were talking about it but hadnt done it , didnt know of anyone who had done it and couldnt poinbt to any studys about it ............i know someone who doesnt want to be named that tried it and it didnt work .......... for me ..................

One still has to get the ergot alkalods to make it and thats the difficult part ........ from what i`ve read .......

dream0n · « **Reply #7 on:** June 13, 2011, 01:31:55 AM »

Getting Ergot Alkaloids from seeds, certain types of grasses, and other fungi are 'easy'. The most easy being seeds. Yes the yields suck, but hey you get your LSA when you hydrolyze all of the other Alkaloids.

With a theoretical yield of 3 grams from 1 kilo of seed, but for practicality's sake we shall say only 80% of that makes it to the pure product.. just about 9mmol. of LSA.
It's good to question the validity of things, It forces people to reason and not to be spoon-fed.
The legality of the analogues is something noted that I do not find referenced, and will completely disregard.
I don't suppose many people will come out and say they have tried it, but there are notes on dosage.. so I assume there has been some bio-assays done.
-Second Edition of Psychedelic Chemistry by M. V. Smith.

Quote

I want to emphasize that "legal acid" can be obtained if other amines are substituted for diethylamine in LSD synthesis.
These other lysergamides should give identical trips, but most of them are less potent than LSD.
Precise potency data do not exist, so it remains for an enterprising chemist to gain immortality by adding each of the following amines (and any others that come to mind) to LSD, separate aliquots of the final step of LSD synthesis (they could easily be done simultaneously), isolating the tartrates and assaying them for potency: piperidine, diisopropylamine, ethylisopropylamine, ethylpropylamine, methylethylamine, methylisopropylamine, tetrahydrooxythiazine, tetrahydroisoxazine, dioxazole, 2-ethylmorpholine, 2,5-dimethyl (or dimethoxy) pyrrolidine, cyclo-butyl-amine, cyclopentylamine, etc.
Published potency data expressed as a fraction of LSD activity follow: pyrrolidide (1/20), dimethylamide (1/20), morpholide (1/10 or 1/3), ethylpropyl (1/3), dipropyl (1/10), methylethyl (less than 1/10), methylpropyl (less than 1/10).

Also, Tihkal has a bunch of possible analogues in its LSD entry.

[Edit] See here for common precursors, etc. http://127.0.0.1/talk/index.php/topic,155.0.html [Edit]

aniracetam · « **Reply #8 on:** June 13, 2011, 04:00:51 AM »

Quote from: dream0n on June 13, 2011, 01:31:55 AM

Getting Ergot Alkaloids from seeds, certain types of grasses, and other fungi are 'easy'.

you must have not tried the fungal route, it's probably the most involved...and potentially, most efficient; yields can be
quite impressive, to say the least..
but I wouldn't call it easy. the toughest part is inducing/maintaining expression from a mutated saprophytic culture of a certain strain.

seeds are for the birds.

dream0n · « **Reply #9 on:** June 14, 2011, 03:04:42 AM »

I agree that the fungi route is most worth while and well, not easy... Extraction is the easy part, sorry for that bit confusion on my part.
For smaller amounts I suggest that it is economical to buy & extract from seed.
-Well then I am a bird

-
I might be able to obtain kilos of wood rose seed for around 200 USD per; I think that is a solid price that places the highest cost of doing the synthesis on the lab equipment. (Which is one thing that I have only some idea of what would be needed).

Can anyone find/make a good list of necessities (labware) for this extraction, synthesis, and purification (chromatography, but specifically what models might be better. etc.). -This could go in the acquisition section-

Balkan Bonehead · « **Reply #10 on:** June 14, 2011, 12:20:50 PM »

I am really curious if sodium pyrosulfate would work as a condensing agent here: http://books.google.com/books?id=1x04AAAAYAAJ&pg=PA83&dq=pyrosulphate&hl=en&ei=F1D3Tb6YHaTkiAKGhNT9DA&sa=X&oi=book_result&ct=result&resnum=2&ved=0CC4Q6AEwAQ

The use of mixed anhydrides of lysergic and sulfuric acids has made me wonder if pyrosulfate in an aprotic solvent like DMSO could affect the same result. Of course, the hardest part is getting the lysergic acid.

oldguy · « **Reply #11 on:** June 17, 2011, 12:43:31 AM »

Back in the early-mid 1970s I ran into a chemistry graduate student at Harvard. He told me how he had done LSD and God told him to spread LSD throughout Harvard. His roommate, a grad student at the business school, evidently told him to spread LSD throughout every college on the east coast, and that's what happened. The tiny little window panes were particularly amazing, people that had tripped hundreds of time had never seen a clear cosmic light like that.

Unfortunately, I wasn't bee enough then to ask him about synthesis, chromatographic separation or crystallization. I do remember him telling me he got the lysergic acid from Cuba. Don't know if Fidel and Raul have kept that pipeline open.

overunity33 · « **Reply #12 on:** June 17, 2011, 02:40:59 AM »

Peptide coupling is nice but requires anhydrous LA... What do you guys think about the moisture sensitivity of this reaction, might it be a little forgiving?

aniracetam · « **Reply #13 on:** June 17, 2011, 03:50:56 AM »

yea, it'll just be a bit dirty. moisture isn't going to make it ignite or anything, the peptide-coupling route
is considerably safer than other methods.

letters · « **Reply #14 on:** June 17, 2011, 08:58:12 AM »

classic newbie thread. this has been discussed ad-nauseam in all the drug forums. there in absolutely no way you will get "90% from Ergine". Ergine is an amide. pybop can not be used to alkylate it. you will need to hydrolyze the amide in alkali conditions, and only then use pybop to amidate the carboxylic acid.
the synthesis is vulnerable to impurities in the starting lysergic acid resulting from impure starting alkaloids and less then perfect lab technique in the purification of the lysergic acid. Casey's paper seems solid. Nichols' paper even more so

HBWR seeds come in various qualities and potencies. 200USD per k is too cheap to be the good kind. Extraction can be done by wetting the seeds with ammonia and doing multiple shakings and separations with diethyl ether. Acetone/1% tartaric acid is also reported to be a very good extraction medium for HBWR and MG seeds.
dont fool yourself into thinking you can just extract the seeds this way, evaporate, throw into some NaOH and get lysergic acid. Rigorous cleaning of the alkaloids is necessary or you will only get gunk. If you use good quality HBWR seeds which contain a large amount of Ergine/Isoergine compared to the other alkaloids then you can use solubility manipulation to separate these 2 from everything else. if you are serious, read up the literature in the university library to find out how.

dream0n · « **Reply #15 on:** June 18, 2011, 02:47:48 PM »

I will fully agree that a yields most surely will not be as good as published here, and that chromatography purification technique must be used on the LA to begin with if you want to get decent yields from the coupling. Yes that number per kilo is from India not hawaii.

way more expensive and could not find a decent looking site that sells kilos of HBWR seeds. Also, props to letters for pointing out; that it is described in a best case scenario and that iso-ergine needs to be converted via routes that are here:

Quote

Isomerization of iso-LSD into the active LSD-25
USING THE RED LIGHT:
Dissolve the synthesized material into the minimum amount of ethyl alcohol.
Mix a 4 Normal solution of potassium hydroxide in ethanol. The amount of solution needed is twice the volume of the iso-LSD/ethanol solution.
Add the two solutions together and let the mixture sit for 4 hours at room temperature.
Neutralize the mixture with dilute hydrochloric acid, then make it slightly basic with ammonium hydroxide.
Extract the mixture with chloroform, sparate the chloroform layer, and extract this four times with a 25% volume of water.
Evaporate the chloroform in a vacuum. Discard the water extracts. The material left after evaporation a mixture of iso-LSD and LSD-25, the active LSD predominating.
The mixture may now be separated by chromatography and the iso-LSD again isomerized by the above process.

This has been cross posted in many places, and is fairly good. Again, Reading the literature is the best thing to do.
This process should work for both LSD and LSA, though the LSA must be hydrolyzed to form ergine and isoergine.

aniracetam · « **Reply #16 on:** June 18, 2011, 04:48:13 PM »

Quote from: letters on June 17, 2011, 08:58:12 AM

classic newbie thread. this has been discussed ad-nauseam in all the drug forums. there in absolutely no way you will get "90% from Ergine". Ergine is an amide. pybop can not be used to alkylate it. you will need to hydrolyze the amide in alkali conditions, and only then use pybop to amidate the carboxylic acid.
the synthesis is vulnerable to impurities in the starting lysergic acid resulting from impure starting alkaloids and less then perfect lab technique in the purification of the lysergic acid. Casey's paper seems solid. Nichols' paper even more so
HBWR seeds come in various qualities and potencies. 200USD per k is too cheap to be the good kind. Extraction can be done by wetting the seeds with ammonia and doing multiple shakings and separations with diethyl ether. Acetone/1% tartaric acid is also reported to be a very good extraction medium for HBWR and MG seeds.
dont fool yourself into thinking you can just extract the seeds this way, evaporate, throw into some NaOH and get lysergic acid. Rigorous cleaning of the alkaloids is necessary or you will only get gunk. If you use good quality HBWR seeds which contain a large amount of Ergine/Isoergine compared to the other alkaloids then you can use solubility manipulation to separate these 2 from everything else. if you are serious, read up the literature in the university library to find out how.

seeds are a newb route, and the alkaline hydrolysis step has been thouroughly discussed.
if you really want to make yourself useful, join the claviceps research group, and get experimenting. it's a more efficient method, one that certain bees scoffed because they obviously have no experience in applied microbiology.

Author Topic: LSD synthesis via peptide coupling (Read 362 times)

dream0n

LSD synthesis via peptide coupling

The Lone Stranger

Re: LSD synthesis via peptide coupling

xxxxx

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akcom

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aniracetam

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dream0n

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The Lone Stranger

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dream0n

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aniracetam

Re: LSD synthesis via peptide coupling

dream0n

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Balkan Bonehead

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oldguy

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overunity33

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aniracetam

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letters

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dream0n

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aniracetam

Re: LSD synthesis via peptide coupling