Total Synthesis of Lysergic Acid (LSD Precursor): Retrosynthesis & Mechanisms (Hofmann, Woodward)

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Welcome to this channel on organic synthesis. This is not an experimental channel showcasing chemical experiments but rather will deal with theoretical discussions of syntheses of important chemicals and interesting natural products. If you are not familiar with organic chemistry, do not expect to understand everything I'm talking about. Please consult the literature, the myriad of youtube videos about basic chemistry or just Google.

In this first video, we will cover the history of lysergic acid, a LSD precursor, its first total synthesis and a modern approach (with increasing difficulty).

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00:00 Introduction about the significance of lysergic acid derivatives and importance of natural products
00:49 Overview
02:09 History preceding the synthesis of lysergic acid about the work of Albert Hofmann at Sandoz (first semisynthesis)
04:12 First total synthesis by chemists at Lilly & Nobel laureate Robert Burns Woodward. This synthesis employs reactions encountered at in the first two years at an undergrad level.
12:40 Modern approach by Prof. Ohno at Kyoto University. This contemporary synthesis relies on organometallic chemistry and more advanced retrosynthetic disconnections. This part contains a short discussion of reaction mechanism.
18:10 Closing comments

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 Youtube.

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 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)
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Feel free to check out my other videos in case you're interested in chemistry and science!

totalsynthesis
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man, chemistry really did peak in the 50s and 60s

viktorprypoten
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the world needs mass amounts of bike day chemicals. humanity needs more chemists

lumpygasinavacuum
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I'm a retired R&D chemist and find this a nice refresher.

edwardarruda
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As a chemist in industry, this is fantastically interesting. I found the depth of explanation of each time period most interesting, it is fun to think about chemists not so concerned with PPE 🤣🙏

prostrongmanzack
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Straight called out for watching this while tripping. You earned a like.

trevortyleris
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"..Or some random bloke just tripping acid, I hope you enjoy this video"
Me on acid watching this video: ¤_◇ I am chemical

yourfaceable
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keep up the good work buddy, honestly this is what i want to see on youtube, will support ur channel :)

elitchemist
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high quality video..
no music no bullshit...
it's hard nowadays to find such seriousness in youtube.

ivanmassimo
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The best chemical ever synthesized. Not meant for daily or even monthly consumption but for when you need a new perspective.

tylersmith
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Excellent. Wish I had a teacher like you when I started grad school in 1987.

ronaldpeanut
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Watching the 2011 synthesis I can't help stare in awe at our predecessors ingenuity. Beautiful video!

juanbisceglia
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Enjoyed the video. I feel stereoselectivity is of paramount importance while discussing total synthesis in this day and age and maybe you can ask your viewers who find it difficult to skip to another point in the video.

This is a very good initiative and I sincerely hope you will inspire many thousands of students to pursue Organic chemistry.

abhijitha
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I took ochem to the 400 level, and after 8 years, I can recognize some of what you are saying. I understand the drawings. I dont know every or any of the reaction type or mechanisms behind them. It would be cool if you had the molecules move around and have arrows moving around to show the reaction. I like the history aspect, old, middle, new. I think it was great, I will watch more.

donbredorouso
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Random bloke part made smile. Thanks for the shout out

seancady
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Me being an A level student who has only just done Friedel-Crafts reactions thinking I would have a chance to understand the mechanisms.

jedwalsh
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Complicated and history driven videos are a delight.

Rayselddiaz
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Happy I found this. I want to study the effects of LSD analogs, specifically AL-LAD, and try to understand why differences and similarities may occur between them. Research so far has been...groovy ✌

lumiii_-
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This video is kind of old now but as an undergrad chemistry student, this video was perfectly suited for my knowledge level, love the video.

williamguthrie
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I find it fascinating synthesizing complex drugs like this

koukouzee