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Peptide coupler method for LSD production...


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#1 Guest_pissybee_*

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Posted 31 March 2006 - 10:14 PM

http://img175.images....34929pc0cw.jpg

This were comments on the article but were posted in the file sharing area...........java

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Cherrie Baby
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Posted On: Dec 18 2005 At: 10:02:41 PM | Reply Link
The article above by Casey Hardison, The Entheogen Review, Vol.
XIV. Number 1 - Autumnal Equinox 2005, surely has an error in it. In the experimental section he talks of "N,N-diethlmethylamine". Surely it should be "di-N-ethyl-mono-N-methylamine" (thanks KT!!). Must be a type-setting error there.

Here is the OCR (with the error corrected). Let us hope the OCR has not introduced new errors!:

The Entheogen Review, POB 19820. Sacramento. CA 95819-0820. USA - 94
Volume XIV. Number 1 - Autumnal Equinox 2005

Novel Condensation of d-LA into d-LSD via PyPOB
by Casey William "Freeblood" Hardison

Although the following piece is technically oriented, we feel that it will be of intellectual interest for those with an understanding of chemistry. Author Casey Hardison is a longtime friend to staff members of The Entheogen Review. His article "An Amateur Qualitative Study of 48 2CT-7 Subjective Bioassays" appeared in the MAPS Bulletin 10(2):11. He is currently serving a 20-year term imprisoned in the United Kingdom, one of the harshest punishments delivered in the U.K.: seven yean outside the 1978 "Operation Julie" sentence of Richard Kemp, and six years outside the guidelines set by the 1996 Joseph Hurley case. We encourage ER readers to correspond with Casey via the address below.

A recent publication by Dr. David E. Nichols (Nichols et al. 2002) on the isomeric lysergamides of demethlazetidine catalyzed a revolution in the realm of clandestine LSD synthesis. I do not know if Dr. Nichols is to be credited with the first use of PyBOP for lysergamide condensation, as theoretical discussions on the use of a variety of peptide-coupling reagents have been occurring on The Hive (www.the-hive.ws) and Rhodium (www.rhodium.ws/chemistry/et2lsd.txt) web sites since 2001.

In early 2004, I engaged Dr. Nichols in a theoretical discussion as to his expected limits on scale-ability and it was clear that he did not know, as he is limited to NIDA quantities of the lysergic acid, i.e. > 250 mg.

After studying Dr. Nichols' papers and the Internet, and doing further book research on peptide synthesis (Coste et al. 1990), I conducted a series of experiments to determine the limits and parameters of the reaction, i.e., the best solvent, the best tertiary scavenger amine, the best sequence of introducing the reagents, and the most effective reaction time.

I worked with several solvents, but I found CH2Cl2 to be most suitable, as it evaporates easily and keeps the reaction temperature low.

I worked with several tertiary amines, but di-N-ethyl-mono-N-methylamine added slowly after the dry lysergic acid gave the most effective results and work-up.

I varied the reaction time between 30 to 120 minutes; however, I am of the opinion that the reaction completes in less than one hour. All reactions were conducted under a 15w red light, in an Argon atmosphere, and with dried Sigma-Aldrich solvents and reagents.

Experimental
2.80 grams of lysergic acid was added to 100 ml of magnetically stirring CH2Cl2. To this was added 1.81 grams di-N-ethyl-mono-N-methylamine and the solution was allowed to stir for five minutes. Then 5.70 grams of PyPOB was added and the solution was allowed to stir for an additional five minutes. Then 0.84 grams of diethylamine was added and the reaction was allowed to stir at RT for 60 minutes.

The reaction mixture was quenched with 100 ml of 7.5M concentrated NH4OH, the layers were separated and the aqueous phase was then thrice extracted with 30 ml CH2Cl2, the organic layers were combined and rotary evaporated at 35°C under high vacuum.

The residue was dissolved in 40 ml of cold saturated NaHCO3 and extracted thrice with 20 ml EtOAc, the organic layers were combined and washed with deionized H2O, brine, and then dried over MgSO4, filtered and rotary evaporated at 40°C under high vacuum to a constant weight. Yield 3.13 grams before chromatography, 93%.

Another run of 5.12 grams lysergic acid with the same amines, equivalents, and times, yielded 5.55 grams after chromatography, 90%.

The Work Ends
It is unfortunate that as I was perfecting this reaction, I was under police surveillance, brought to the attention of the London DEA by an informant in the United States. Donations accepted and desired (checks, money orders, books, letters, love, etc.);correspondence can be sent to:

Casey Hardison • POWD LH5330

Her Majesty's Prison. Parkhurst, Newport, Isle of Wight, PO30 5NX, England

------------------------------------------------------------------------

Ionium
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Posted On: Dec 22 2005 At: 10:42:14 PM | Reply Link
Quote:
Originally posted by Cherrie Baby

The article above by Casey Hardison, The Entheogen Review, Vol.
XIV. Number 1 - Autumnal Equinox 2005, surely has an error in it. In the experimental section he talks of "N,N-diethlmethylamine". Surely it should be "di-N-ethyl-mono-N-methylamine" (thanks KT!!). Must be a type-setting error there.

Here is the OCR (with the error corrected). Let us hope the OCR has not introduced new errors!:


It apparently hasn't. However, there are a few other errors in the original text, I found 2 more you might want to correct too(the bold underlined words):


Quote:
Entheogen Review wrote:

A recent publication by Dr. David E. Nichols (Nichols et al. 2002) on the isomeric lysergamides of demethlazetidine catalyzed a revolution in the realm of clandestine LSD synthesis.


That should read "dimethylazetidine".

Quote:
Entheogen Review wrote:

In early 2004, I engaged Dr. Nichols in a theoretical discussion as to his expected limits on scale-ability and it was clear that he did not know, as he is limited to NIDA quantities of the lysergic acid, i.e. > 250 mg.


This paragragraph only makes sense when read as "i.e. < 250 mg.", otherwise Dr. Nichols would indeed have known the answer to mr. Hardison's question. Also, the NIDA limit must obviously be a maximum amount, not a minimum as the uncorrected text implies.

Thank you for sharing the OCR'ed text!
---------------------------------------------------------------------------------------

Thanks for posting that, I absolutly loved the article and its great to see any corrections, I think im going to write that right in my copy of the ER.


What do you guys think about this? its something I saw over an another forumn, ill just post the whole thing as I have it.




LSD Synthesis: No PhD required
__________________________________________________ _______
"Makoeyes method of practical LSD production:


1) A/B extraction of HBWR seeds (850g). yeild: 2.5g misc ergot alkaloids
2) Hydrolysis of extracted Ergot alkaloids. yeild: 1g Lysergic Acid
3) Distilation of DEET to Diethylamine. ; ; ; yeild: 2g Diethylamine
4) Coupling of LSA with Diethylamine via PyBOP. yeild: 1.7g D-Lysergic Acid Diethylamine
(some given stuff is left out, this is discussed later)

step 1
A/B extraction of HBWR seeds (850g).
1) Wash/dry seeds... Powder 850g of seeds in a clean blender or coffie grinder. Air dry the resulting powder.
2) Submerge podwer in VM&P Naptha (petrolium ether) in a flask, stopper flask, shake vigorusly, let sit for 2
& ; ;nbs p; days in a dark place shaking every once in a while.
3) Vacume filter, save/dry resulting mush (dry in vacuo).
4) Submerge powder in ahydronus MeOH in a flask, stoper flask let sit 2 days in a dark place shaking every once in a while.
5) Vacume filter, save the MeOH this time. Revome solovent in vacuo.

This is the gunk that morons across the web will debate all day, is it lsd? (no) is it lsa? (kinda) Is it an amine or an amide?
(amide) Is it active? (kinda) It made my friend vomit!(your friend is a dick) it must me cyanide!! (you're a dick) ... on aleged
toxicity: to make along argument null, yes there is something like cyanide in the seed, is it cyanide?... no, it has some
Cyanogenic glycosides in the seed coat, alot of seeds (apple) do. will it kill me?... (no) will it make me sick? (yeah probably,
thats why we extract) what if im lazy? (dont eat a lb of raw plant material, you will be fine)

[snip] % of Total alkaloid % dry seed weight
Ergine 22.68 0.136
Isoergine 31.36 0.188
Ergometrine 8.20 0.049
Lys. alpha-OH-ethylamide 5.79 0.035
IsoLys. || 3.98 0.024

Well, cince we started with HBWR , there is some LSA-111 pressent, not alot, (~.03%) most of it is ergot-type alkaloids, manny of
these these are amides (meaning they are derivatives) of LSA, after you split them with water (hydrolyze) your left with LSA-111
and ISO-LSA-111. lysergic acid means the organic acid you get when you split ergot. the aformentioned crap yeilded form the
procedure above will be gunky and off color if you proceed with it you wont yeild a whole lot. But, maby you dont want alot,
maby you just wanted enough to trip on, whatever, sounds like waste of money, and forget about selling it. I sudjest
purification of this rough extraction for better yeilds down the line. JiJo, SiCo and the like... (junk in Junk out Shit in Shit
out)"You can't piss into a Mr. Coffie and get "Tasters Choice""-commentary on Waterworld
(stupid movie... I kinda liked it ... SHIT!...)

step 2
Hydrolysis of extracted Ergot alkaloids.
1) Dissolve 2.5g of the alkaloid in 22 ml of 1 M methanolic KOH solution (this is made by dissolving 1.4 g of KOH in 25 ml of
& ; ;nbs p; dry methanol).
2) In a 1 1iter evaporation flask (heavy walled construction) immediately Evaporate the methanol off.
3) Add 40 ml of 8% aqueous (water) KOH solution to the residue and boil for one hour under a slow stream of nitrogen that is
& ; ;nbs p; allowed to flow through a small orifice for exhausting purposes.
4) Cool, acidify with dilute sulfuric acid, and shake in a separatory funnel with 1 1iter of dry ether. keep the lower aqueous
& ; ;nbs p; layer.
5) Vacuum filter. Wash the precipitate with 2 ml of dilute sulfuric acid.

This is lSA and iso-LSA ('bout 20% iso) time to brake out the column. im not gonna go into how to opperate a column here, your
big boys, and if your not your in over your head as it is. chromatography: yes its a BITCH and no theres not a real way arround
it. i happen to think its fun, but i havent ben at it a grate while, perhapse the magic has faded for you, perhapse im a nerd.
who knows. any way arround it your gonna' wanna' run a column. there will be 2 major floressent bands (oh yeah you need a black
light, (long wave) dont leave it on the whole time or anything. just check your bands) the greater is LSA, the lesser is
Iso-LSA. Colect them both in seperate collection flasks, you can convert the Iso-LSA to Lsa or just discard it, whatever,
point is you want LSA for the RXN not its isomer.

+

step 3
distilation of DEET to Diethylamine.
1) Mix DEET with an excess of 10-20% aqueous NaOH.
2) Distill, collect the distillate in dilute HCl.
3) Evaporate HCl to get Diethylamine Hydrochloride.
(to circumvent this stage just buy some Diethylamine HCl, its pretty suspect tho)

step 4
Coupling of LSA with Diethylamine via PyBOP.
1) Dissolve 1g LSA in ahydronus Toluene at RT.
2) Add 1.05 g PyBOP.
3) Add 2g of diethylamine stir reaction at RT until it goes to completion (15min-2hr).
4) Remove the solovent under vacuum.
5) Load residue form step 4, Toluene and saturated NH4OH in to a sep. funnel.
6) Wash the organic layor with NaHCO3 (or NH4OH) and H2O.
7) Saturate with NaCl.
8) Dry over MgSO4.
9) Filter and concentrate in vacuo to remove the solvent and excess diethylamine.
10) Converte to the tartrate salt.


lets talk about purification. obviusly your chromatography column is your best friend, mine is... we play poker on thursdays, him and
my seperatory funnel... (if you dont FUCK this up you will too... very interesting, *HINT* lab glass with open stopcocks will bluff)
but there are some *other* purification methods you damn well better know too. extraction, recrystallization etc. but you already knew
that right?

Purification of the alkaloid extraction (product from step 1):
1st off repetition of the procedure would help.
All basic extraction rules apply here, 3 is the magic number.
its more important to purify step 2,

The LSA yeilded from step 2 to can be purified in this mannor:
1) in a seperatory funnel shake with 2 x 400ml 2 mol NH4OH (in ethanol)
2) combine the extracts and evaporate in vacuum to give LSA.

above is a work in progress its based on standard peptide synthesis techniques"

Peptide coupling is standard, plain, vanilla organic chemistry. So I've got science on my side, who's on yours? Next time try not to be an asshole, and besides my internet dick is bigger than yours anyway.




ok kids. i'll let the cat out of the bag. no need to culture ergot.
Aquire HBWR seeds, crush, dry in dessicator (or similar). Defat by extracting thoroughly with nonpolar (preferably low-boiling, like DCM), remove solvent traces with vacuum, extract *very* thoroughly with lots of dry methanol (maybe using vacuum soxhlet), concentrate in vacuo, then column chromatograph to isolate LSA, hydrolyze LSA to lysergic acid (KOH). Separate iso- from lsyergic (HNO3) and isomerize with KOH. Combine the two portions of "normal" (non-iso) lysergic acid, and separate optically pure d-lysergic acid via tartrate. Store cold/dark and under inert gas. Make diethylamine by distilling NaOH and DEET bug repellant . (make sure you have very good purity here, too) Turn off the light - illuminate your work area with candles. Dissolve 1 molar eq. d-lysergic acid tartrate in ice-cold analytical grade DCM (dried over mol. sieves) in brown glass flask under inert gas atmosphere, add 1.1 eq. pyBOP followed by 4 eq. tertiary amine as the free base, stir for five minutes. Then add 2 eq. diethylamine hydrochloride and stir for 3 hours under cooling. When reaction is completed quench with conc. ammonium hydroxide, separate the organic layer, extract 4x with more DCM, combine organics. Wash 2x with ice-cold d.H2O, then 2x with brine (use analytical grade NaCl here, NO TABLE SALT please!) and dry thoroughly with molecular sieves. Place in small evaporation flask (brown glass), rinse sieves 3x with small amount of DCM, and evaporate solvent with a rotovap. Column chromatograph residue to get pure d-lysergic acid diethyl amide. PyBOP is a peptide coupling reagent. almost everything else is really low key in the chem lab. shit, other than a few things most of this stuff could be found in a high school chem lab. this idea was convieved by a person named noodle.


--Taken from wetdreams.ws ( https://www.wetdream...p?TOPIC_ID=1252 )

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#2 Hippie3

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Posted 31 March 2006 - 10:22 PM

i count lsd as a misc. entheogen
so thread should be in this forum.
moved.

#3 Guest_pissybee_*

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Posted 31 March 2006 - 10:23 PM

Name: PyBOP
Category: Peptide Coupling Reagent

 

Product Data Sheet

Product Name


PyBOP;
Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate

CAS No.
128625-52-5

Molecular Formula


C18H28F6N6OP2

Molecular Weight


520.40
Appearance White crystalline powder
Purity (HPLC) 98% min.
Melting Point 152-158 oC (dec.)
TLC Analysis One spot
Loss on Drying 0.5%
300 MHz 1H, 19F and 31P NMR Spectra (DMSO) Consistent
Elemental Analysis Consistent
Solubility Test 1 mmole in 1 ml DMF, resulting in a clear solution
PyBOP® is a fully registered trademark of Merck Biosciences AG in the countries of France, German, Italy, Japan, Switzerland, the United Kingdom, and the United States only.

#4 Guest_pissybee_*

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Posted 31 March 2006 - 10:25 PM

thx, Hip... :bow:

#5 Guest_freakachino_*

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Posted 31 March 2006 - 10:37 PM

Thank you PB for the post. Good reading, I've got to go through it a few more times, but thanks for the post!

:bow:

#6 swine

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Posted 31 March 2006 - 10:46 PM

thank you for the info on PyBOP (POB?)

#7 Jonah

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Posted 02 April 2006 - 12:59 PM

what are the industrial uses for PyBOP? Any use in hobbyist electroplating or photography or anything like that? And lets see, diethy-methylamine.... from DEET, right? That could be used for DMT too, i think. There's reference to something similar to that book by prof. buzz

#8 Guest_pissybee_*

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Posted 02 April 2006 - 02:11 PM

Seems PyBOP is the only peptide coupler I can find listed anywhere, so I believe the PyPOB is a typo in that article.. I am unsure exactly what the industrial/commerical uses of PyBOP are, but I'll try and find out...

#9 Elf Salvation

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Posted 02 April 2006 - 09:57 PM

what are the industrial uses for PyBOP? Any use in hobbyist electroplating or photography or anything like that? And lets see, diethy-methylamine.... from DEET, right? That could be used for DMT too, i think. There's reference to something similar to that book by prof. buzz



DEET-->Diethylamine....-->DET, Diethyltryptamine

#10 Guest_pcsillypj_*

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Posted 04 April 2006 - 12:11 AM

thnx for sharing this info with us pb....:bow:
i just love LSD...was my first drug i ever took and
is still on the top of my list...:D

#11 Guest_lost_onabbey_rd_*

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Posted 04 April 2006 - 12:54 AM

APPLICATIONS
Coupling reagent for solid-phase peptide synthesis without forming carcinogenic HMPA as by-product.
------------------------------------------------------------------------
An alternative coupling reagent to BOP which does not produce carcinogenic by-products.
------------------------------------------------
2.1.2. O-Benzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate (PyBOP)





PyBOP (14) and BOP (13) were commonly used coupling reagents in N-acylation, especially in peptide synthesis.38 PyBOP enables the preparation of phthalimides from the corresponding primary amines, including amino acids, in two steps.39

1-Hydroxy-4-nitro-6-(trifluoromethyl)benzotriazole phosphonium salt (CF3-NO2-PyBOP or PyFNOP) (15), a modified PyBOP reagent, has been described as highly reactive and efficient for the N-acylation of N-methyl amino acids (Scheme 8);40 earlier work has indicated that DCC/HOBt and BOP show less efficiency in octapeptide synthesis.41 1-Hydroxybenzotriazole derivatives including PyBOP are comparable in reactivity and yield for the N-acylation of N-methyl amino acids.

http://www.arkat-usa...es/image017.gif

---------------------------------------------------
2.1.1. O-Benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP)





BOP (13) was prepared by Castro in 1975 by mixing tris(dimethylamino)phosphine with 1-hydroxybenzotriazole in CCl4 at -30 °C followed by treatment with KPF6.35 In this paper, protected amino acids were coupled with amino acid esters at ambient temperature in 81 to 98% yield. Another peptide synthesis using 13 at room temperature in the presence of DIEA uses carboxyamidomethyl ester as a carboxyl protecting group (Scheme 7).36 Among most other works, a stepwise solid-phase peptide synthesis using BOP has been described for the preparation of 7–10 amino acid residue peptides using p-hydroxyphenyl propionic resin.37
http://www.arkat-usa...es/image015.gif

i don't really understand all that, but thought somebody might find it useful
lost

#12 Guest_lost_onabbey_rd_*

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Posted 04 April 2006 - 12:57 AM

http://www.genscript...cgi?code=C01572

#13 Guest_pissybee_*

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Posted 04 April 2006 - 01:01 AM

Good shit lost!! :D

#14 lyqwyd

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Posted 12 April 2006 - 06:21 PM

makes me wish i had some glassware/ access to the chem lab at a college. those are some pretty simple procedures, all of which i know how to do... and the chemmies are sooooo commonplace! good job noodle... and thanks PBeester!

#15 loochypooch

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Posted 12 April 2006 - 07:42 PM

I have no clue, is this like BYOB?

:eusa_doh:




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