LSD Synthesis in 7 Steps (Educational) | Lysergic acid, organic chemistry, reaction mechanisms
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- Опубліковано 24 лип 2024
- This video does not explain or suggest how to make drugs, and is purely educational and theoretical. A team of chemists recently reported a synthesis of lysergic acid, the precursor of the psychoactive drug LSD, in only 6 laboratory steps. In this video, we will learn why LSD-like scaffolds are of interest to modern drug discovery and look into the chemistry of this short but sweet synthesis.
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Reference:
- Six-Step Synthesis of (±)-Lysergic Acid; doi.org/10.1021/acs.joc.2c02564
- Identification of Psychoplastogenic N,N-Dimethylaminoisotryptamine (isoDMT) Analogues through Structure-Activity Relationship Studies; doi.org/10.1021/acs.jmedchem....
00:00 Why science cares about LSD (lysergic acid diethylamide)
02:11 High-level retrosynthesis of lysergic acid
03:13 Forward synthesis of lysergic acid
06:14 Broader application to pharmaceutically relevant structures
Disclaimer - This channel does not provide medical advice!
No information on this channel is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of information on UA-cam.
Some recommended books on organic synthesis:
- Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge)
- Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis)
- Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions)
- Nicolaou et al; Classics in Total Synthesis 1-3 (the ultimate total synthesis trilogy)
- Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life)
- Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures) - Наука та технологія
Here's a 3D model of LSD you can play with yourself:
total-synthesis.com/lsd-synthesis/
Thanks to my supporters! www.patreon.com/totalsynthesis; instagram.com/totalsynthesis_official/
You know what this does suggest? that you're awesome
I would have guessed the Adams scale, but I guess not. I do know after 3000 micrograms I did not shake my head violently but I did feel tiny micro seizures but they were of no consequence. Kn owing the hum,an saturation level is only 2000 micro grams, I had to try just once. It was very enlightening, and pretty visual too. About 300 feet after leaving the wooded area where I lived I was still using my hands to clear any branches, knowing full well they weren't actually still there but that other voice in our head made me just to be safe. Love that drug, ever since 1970. Now where i live I can carry it and not worry about getting arrested for it, same with cannabis, and I feel much better with those laws in place. Harm reduction first, everything else afterwards.
Oh, and educate yourself about drugs instead of "just say no" BS that has the opposite effect and know how they work if you are planning on using them, be smart and be prepared to make good decisions and then you can enjoy them too. Education is all we need...and some cash helps too.
@Drampa Dreg, where do you live that L, and cannabis is legal? Portugal? Thanks. Peace.
@@drampadreg1386 Am I reading this correctly?
As I understand it; the typical dose is 100
It always irritates the shit out of me when people who have never done psychedelics, call it "hallucinating". They aren't hallucinations... Especially DMT... You can make it (so can I) and I appreciate that. But the nerds who build the rocket, shouldn't presume to tell the astronaut what space is like from earth... I realize this is what you have been taught, but now you know better.
We're now all on a list... The cool list 😎
As a teen in the 70’s we were bombarded with the message that LSD would cause “flashbacks.” I took plenty of window pane and blotter as did all of my friends. Not one of us has ever gotten the promised 2 for 1 gift of a flashback. I for one feel cheated and lied to.
I'm on a permanent flashback, it iz what it iz
@@infinityiznow Lucky You! I’m afraid that I may need a refresher dose.
@@davebennett4087 tonasket barter faire, be there or be square
I’m an analytical chemist, and have nothing but admiration for organic chemistry like this. Pure art and science 👌🏻
You have no idea how these chemistry videos boost my knowledge in chemistry which is essentials for my videos and my experiments in the lab. Thanks.
That's lovely to hear. Good luck :)
xd
Nice bait, fed
Psilocybin saved my life. I was addicted to heroin for 15 years and after Psilocybin treatment I will be 3 years clean in September. I have zero cravings.
This is something that truly needs to be more broadly used in addiction treatment.
"Is it a good trip"
"Idk lemme see how hard my mouse shakes"
😂😂
Beautiful!
🔥🔥🔥
@@totalsynthesis ayy there it is, H-milton in the house
The legend himself!
the man
👁️
I kind of get why they want to take away the hallucinations in a medical type setting but I find that it’s a part of why it works so well for me and my mental health. There’s something about being completely detached from reality that lets me further examine myself in ways my conscious mind can’t. Just doesn’t seem as beneficial
I am sorry that information is not of higher demand in this day and age. You deserve the proper reward and recognition for your hard work and it shows your virtue for knowledge, doing it regardless.
Thanks for highlighting our lab's work!!
Oh dang! 👏 Hope the simplified overview here still did the great work some justice
@@totalsynthesis Certainly! In our opinion, the best approaches should not take much time to summarize. We are very excited about where this initial work is going to take us towards making translational inroads into novel psychedelic derivatives :)
Currently in orgo 2 planning to major in orgo eventually. But damn, to think of all these crazy reagents and knowing the mechanisms behind them is intimidating yet still interesting
What’s crazy is they teach these reactions pretty early in organic. Crazy to see every come together
This is actually the research I'm performing now, the synthesis of cyclic thiol ring structured tryptamine derivatives for use in neurodegenerative disorders. The goal is to have the product have a very profound neuroprotective effect without activation of the hallucinogenic response. Facinating field.
Wow what a coincidence. Thats awesome
As both me and my wife suffer from trigeminal neuralgia I'm very interested in this. The non-psychedelic tryptamine derivatives we've tried seem to function well as preventatives but nothing stops an attack in it's tracks like a threshold dose of nn-DMT. It's had me wondering if a degree of psychedelic activity is actually required for tryptamines to work on current attacks.
@@EddieTheH Neuralgia is a very difficult condition to treat, and can be viewed in a variety of ways. The most fearful of any diagnosis is the complete death of the neurons in the area (such as in burn cases), however mild to moderate can be treated/go into remission with some drugs and therapies. Psychedelics don't seem to influence peripheral neurons, but strongly promote neuroplasticity and neuroprotection in cortico-regions in the brain, primarily in the Prefrontal cortex. Hyricium (lionsmane) has been found to be a tremendously potent activator of Nerve Growth Factor, and I believe it has some of the greatest promise for peripheral neuropathy (when paired with another drug like gabapentin). Last but not least, alpha lipoic acid has been used to revert damage from diabetic neuropathy with great promise. Certainly best to look into all of these.
@@EddieTheH I would also suggest looking into the work of Dr. Jason Wallach into NMDA antagonist derivatives and neurotrophic factors.
Having indulged in copious amounts, one of the most intriging fetures of lsd was always i could have my inter monologue sound like any person ive ever heard before . I always thought this could be very helpful in therapy along with lsd ability remove egos
Everytime I've ever took acid it was a very positive experience that improved my mind but also warped it just as much. I can't say I would change anything. I'm better for having taken it
"Practical LSD manufacture" by Uncle Fester gives you a cool run down. Talks about the old skool methods
0:37 This is what I wanted to know for a long time! Measuring how trippy a substance is. However, on the internet I never found anything related to this. People always talk about synthesis but never talk about how to find out about the mechanism of a drug's action.
Now you have read my comment I think you should make a whole video only on finding mechanism of action.
I laughed out loud IRL when he said they went by how much/hard mice shook their heads around. Lol. I can just imagine some mice going WHOA THE COLORS MAN. while their heads are waving around not able to focus on any one thing
Its good to see a fellow swiss putting out high quality educational videos, keep up the great work!
Psychedelics are just an amazing discovery. It's quite fascinating how effective they are for depression and stress..saved my life.
I believe im on every government watchlist at this point 🥰
I love that you upload more frequently! Keep up the good work.
Greetings from another chemist :)
Wow, a total synthesis of ergolines in seven steps?
Man, that's amazing - I remember when I was a kid (late 50s) total synthesis of lysergic acid was what, 25 steps?
As you pointed out, this will open up novel routes
to analogs, both 5-HT2a agonists and perhaps new psychoplastogens -
pretty cool!
Holy shit if I can find a form of LSD with the hallucination removed or especially psilocybin, it could be so useful for my depression and life planning
The trip is the healing part
Nice, didnt know there was such a short total synthesis of LSD starting from an indol derivative.
Forget Lsd, its chemistry that blows my mind , humans are amazing
When I was a kid in the 70's acid was my favorite high. Hitchhiked from Maine to the haight in SF at 17 and wow that was fun. Its a different world now.
I really want to go back and study organic chemistry. Videos like this really help my motivation.
Lol, wanna go dose up some mice to measure "trippyness"? 🤣
Poor mice... lot of respect for Ann and Alexander Shulgin.
Such an interesting video. I am planning on synthesizing this molecule in the future and have been doing some research. I didn't even know about 6-MeO-Dimethyltriptamine neither Bromocriptine. Thank you for making this video explaining the steps and providing useful information for the public. Big like!
Thanks! I don't suggest doing this yourself so would not ingest anything you've created in a lab and treated with chemicals
He may not suggest it, but I do. Ingest anything you think may give you superpowers.
@@inferno7181 lmaoo nice one
it's the 5-Methoxy analog that comes from the Toad, 4-hydroxy is the active metabolite from psychedelic mushrooms, and 4-MeOAc is the synthetically produced acetylated analog of the active 4-hydroxy compound that's a slow releasing DMT trip that lasts ca. 4-6hours.
Good luck. There’s maybe 8 active LSD clandestine chemists in the USA. But please keep me in mind if you can get the precursors and achieve needlepoint Swiss grade L. Please😂
I remember looking up the method once. As chemistry goes LSD seems above intermediate level chemistry
Thanks for the investment in putting these videos together and maintaining the Chanel. This video was indeed very interesting and educational. Well keep up the good work 👍
Thanks man, means a lot!
👍you have a good night,
Your videos are truly one of the best kinds ❤ keep the good work 👍
You did a great job presenting the acid's structure.
Thank you for keeping chemistry alive
Beautiful and concise video! Thank you so much for sharing your knowledge! This is incredibly topical considering the current state of increased openness for real science and research into what some of these long demonized molecules may have to offer us. Subscribed
Now we're all on a watchlist
I love watching the steps and having no idea why it forms in the way it does
1:11 enjoy how such simple structural changes on a molecular level can have such a profound impact on the psychoactive effects of a drug.
Finally the internet will teach me something useful
That brought back nightmares of Organic Chem class. Classroom booring, lab was cool!
The little notation of white dots marking important parts is super smart
It’s crazy what a difference watching this video has after being forced to take OCHEM. Actually pretty interesting, great video!
Thanks!
Looks like I found a new favorite channel. Thank you. I failed Chemistry however it fascinates me. Cheers.
@Bryson Martinez I have Paul's book. Don't get me started on fungus. Thx tho. preachin to the choir
all of them
padawan
ive been growing for 20 years.
I dont know anything about chemistry, but Im still watching lmao
Same, would love to see the actual process. Not that I could recreate it, just wanna watch it
Always a pleasure to see you upload.
1:34 Not so obviously.
Forbidden PHD thesis right there.
Total synthesis is interesting from academic perspective. In practice the starting point of partial synthesis are ergot alkaloids.
Psychedelics definitely has potential to deal with health issues like anxiety and depression , I would like to try them but it's hard to source them here
Here's my latest video if you would like to check out more: ua-cam.com/video/24SpQTYRh38/v-deo.html
Ohhh no, I've crossed eyed listening to this lecture
Gotta love the good ol' "drug a mouse a watch its head shake test" its very scientifical trust me
Great Video, as usual!
Ive always been wanting to find a more streamlined process of lsd synthesis. I really hope that lsd exists in nature due to this. I really think it very easily could due to the diethyl on it not being something too overtly synthetic. With the existance of lsa and lsh it seems possible, alkaloid analysis on plants sadly isnt that common until enough people report effects. Same thing also leads me to beleive mdma could too, mda already exists and the end chain is also present in other natural alkaloid, hell. Even meth occurs in a few acacia species
Olson's work is fascinating, truly envious of that group's talent
Thank you , this is very easy and usefull...... when you have a hell load of different expensive chemicals!
Organic chemistry is the best. I love every aspect of it
I like these chemistry videos, very good explanation. Best regards. 😎👍
Thanks!
I didnt understand like... any of that, but I am definitely interested!
Wow something worth watching for once. This is the mad genius entertainment
Very eductional. Thanks!
Currently studying to be a chemical engineer. I may “use” this one day ;)
Bump. Good work dude. Bound to make some ripples.
Thanks for the video. Maybe you can help answer a question I have. I've researched it and didn't come up with anything. I recently tested two different kinds of blotter with an Ehrlich reagent solution. One perforated and the other unperforated. The unperforated is quite a bit thicker. The perforated has a Felix print on it and the other is just white. They both tested positive but the blotter with the print has a fizz reaction. It looks like hydrogen peroxide on a wound. I was also advised to not store that particular blotter in aluminum foil due to the technique they used to apply the L to the blotter left the top side of the blotter with a crystalin sheen on it that could receive abrasive I guess on it a bit and chip away at the L and diminish the potency of the blotter a bit. The unperforated is stronger and I feel like it is definitely much better in quality. Any idea what is really going on? They originally came from different parts of the world as well not same source.
i truly wonder where one would find Lucy these days....
Thought you were gonna tell us how to make acid, but I simply couldn't understand a single thing you explained.
Gees. As someone who is still an amateur in Chemistry, this is quite overwhelming for the time being. Guess I better get a move on and figure out how all of these reactions work.
I'd love to be one of those mice that get DMT tested on them
I was with you all the way to "This video"
Can you please do Ibogaine!
Also, ?can you explain the equipment and techniques
haha, totally living for ur commentary dude ^_^ subbd
This seems really cool makes me want to study chemistry
Thank you for this...purely educational and theoretical video.
Finally, a suitable synthesis for me
Throw in some geosmin as well for even more sensory overload
Nice piece ..power to you
Excellent education on chemistry to expand healthcare and chemistry knowledge
I'm not super educated about chemistry, so it's surprising and fascinating to me that the plastogenic properties are preserved with certain isomers of e.g., DMT while removing hallucinogenic properties. However....I'm pretty "experienced" you could say, and I'm skeptical about the usefulness of these non-psychedelic drugs because, contrary to what the video suggests, you DO want to trip after taking the pill...that's what gives you the lesson which then guides the neuroplasticity in a productive and healing direction. It's what pulls up information out of your subconscious that needs to come out into the light. (To be clear, all of that is exactly why I believe psychedelics are powerful medicines and not party drugs.) I'd like to know if these non-psychedelic variants have actually been put to clinical use, and if so, as part of what type of process.
They are researching them for example for the treatment of cluster headaches and other conditions in which patients do not need the psychedelic experience (mentally speaking) but need some of the physiological effects. See e.g. clinical tests with 2-bromo-lsd in Switzerland
Thank you Mr. White!
Have fun in the FBI watch list
From personal experince the actual trip when you take lsd is the therapeutic part .
The trippiness isn't a side effect, it's like a dream, a dream in which questions that you have never asked to yourself before, have now answers.
If the groups are in another place (e.g. p instead of o) then the reaction might not work (as well)
Thanks for "educating" me
Love watching theoretical videos such as these
This video is like a fly trap made by FBI
Anyways, love your channel
This one time I took 15 blotter tabs at once.
The first time I ever used LSD I took a Ten strip.
The 1990's was trippy .
Hm yes, I will use this video's contents very educationally 👍👍👍😁😁😁
nice video brah
I love how much your channel is growing. I wish you could make more basic orgo chemical videos that can explain some of this stuff to us noobs a little bit, like a terminology wrap up.
Or maybe I should just wait until next semester to take Orgo I then ill understand what youre talking about :D
Thanks man! Yea doing that would not be interesting to me, and all the basic stuff is out there on youtube etc. anyways so doesnt feel like value add
@@totalsynthesis Sounds good friend :) Your channel fills a niche for the more advanced ochem players. I think a great resource is Poor Man's Chemist, he has done a great job at making his basic o-chem learning playlist.
But please remember, don't forget that your channel's jewel is it's quality over quantity. I like your uploading more frequently but I hope it doesn't into something like That Chemist (no shade to him, but I think the chemical tier list genre has been milked quite a bit now by him. It is pretty useful in learning though).
I want someone to make a chemistry animated channel. Yea it’s a lot of work, but actually seeing bonds change and the mechanics of this in real time 3d models with explanations would be a game changer for those visual people who struggle with walls of text
@@michaelhicks8603 Yes for sure. I would so donate for sometihng like total synthesis' videos in an animated form
@@joaopedroportugal i think that goes beyond my animation skills haha, but good suggestion
It'd be great if you could do one on ALD-52? aka Orange Sunshine
and maybe some 'analog' explanation, how it's still 'trippy' but not LSD
ALso for ideas maybe one on MDMA and other 'alphabet drugs' like 2CI 2CB etc.
I've watched this like 4 times just to hear that line at 1:30 again. Fucking lmao. Love your videos seriously. Informative with a sense of humor =]
I'll admit, this was a bit over my head. But I think the take away is its a good thing?
How many days, following all the reactions and processes correctly, does it take synthesis a finished product of LSD?
I'm guess between three days and a week. Does anyone else have an opinion on this question?
I'm definitely going to use this for educational purposes only 🗿
This is probably one of the most misunderstood substances out their.
A question of curiosity; Why does Robert B. Woodward continue to be credited with Edmund Kornfelds LSD synthesis work? It is called the “Woodward Synthesis” after all? Anyone have an answer?
Is it due to Woodward having some seniority over Kornfeld?? Or Proprietary Authorship?? Why?
"Although it is true that he had trained with Woodward, it was Kornfeld who in fact designed and executed the synthesis. Woodward was an Eli Lilly consultant, and evidently made an important intellectual contribution because he is listed as a co-author on the publication. Yet apparently, because of Woodward's stellar reputation, it has been assumed that if his name was on the paper, it was his work."
(www.nature.com/articles/nchem.558#article-info)
Im highly interested in non-hallucinogenic varieties of LSD. I had spent a good bit of time earlier in my life doing a lot of microdosing and it helped tremendously. I would like to see how well similar chemicals could be made to produce beneficial results, just without the actual trip part. I do know they are testing bromo LSD in Canada at the moment for depression and anxiety I believe. It'd probably do especially well for drug addiction being that depression and anxiety go hand in hand with withdrawal.
Oh remove the OH
with trimethylsiline , does that also turn carboxylic groups into aldehydes? Would triethyl orthosilicate work? Any other equivalent reagent or any other considerations?
I dont think it reacts much with acids/esters
@@totalsynthesis I hoped, but makes sense, resonance stabilizing in the acid, electron configuration of esters + steric effects.
Know if the triethyl orthosilicate useful for alcohols or only the trimethylsiline?
I happen to have some of the former, don't like making the latter, and don't want to break the seal unless I have enough to do with either to use it all at once due to how air sensitive they are.
Ahhh, and I get to add yet another government watchlist to my collection!
Chatgpt help for understanding this
The key bond disconnection that this synthesis is based on is an intramolecular Heck reaction
(the Heck Reaction**: This is a type of chemical reaction where two components, typically containing carbon atoms, are joined together with the help of a metal catalyst, often palladium. This reaction is particularly useful for creating new carbon-carbon bonds in molecules, which is a fundamental aspect of building complex structures in organic chemistry.
Imagine you have two LEGO bricks; one is a small simple piece, and the other is a larger piece with a special attachment point. The Heck reaction is like using a special LEGO connector (the palladium catalyst) to join these two pieces into a new, larger shape. This is similar to how chemists use the Heck reaction to connect two parts of a molecule together with the help of palladium.)
(intramolecular = means the reaction happens in a single molecule, it changes itself, like folding a piece of paper on itself
Intermolecular = means the reaction involves multiple molecules like sticking 2 pieces of paper together)
, the route we are discussing efficienctly traced the intermediate back to this indole containing an aldehyde, which lends itself to nucleophilic addition and other functionalizations.
(Indole**: This is a specific structure in organic chemistry that is a part of many biological molecules. Like a standard building block of Lego. It's a ring structure that's very stable)
(tracing the route of the intermediate means they are looking at the chemical that's partway through its synthesis process (the intermediate, in this case an "indole containing an aldehyde) and figuring out the best way to start making it from commercially available chemicals)
(Aldehyde**: This is a functional group in organic chemistry characterized by a carbon atom double-bonded to an oxygen atom and single-bonded to a hydrogen atom (CHO). Aldehydes are often good targets for nucleophilic addition, where a nucleophile (a molecule or ion that can donate an electron pair) attacks an electrophilic carbon of the aldehyde) aldehyde group is very reactive and can be a site where other molecules can attach easily through nucleophilic addition, it's like putting a magnet on your standard Lego piece so other pieces like paperclips are attracted to it.)
(In summary, the chemist is planning a synthesis based on a reaction that makes a new bond within a molecule, using a starting material that already contains necessary functional groups, making the process simpler and more efficient. This is a common strategy in organic synthesis)
This starting material they found is very convenient as it already has the bromo group for the Heck reaction later on and can be bought commercially.
(The bromo group in the molecule acts like this corner piece, you know many pieces will be able to fit off of it. the bromo group acts as a leaving group. This means that during the reaction, the bromine atom will leave its current position, creating an opening for a new bond to be formed. setting the stage for the Heck reaction to occur effectively.)
Lsd was the 25th compound the doctor made. I wonder if anyone has looked to see what else he made and if t had any benefits. He was trying to make a headache cure.