Organic Chemistry Masterclass: Insanely complex neuroprotective Illisimonin A (+reaction mechanisms)
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- Опубликовано: 10 июл 2024
- ⚠️ This video contains advanced organic chemistry!
Illisimonin A is the perfect quest for synthesis practicioners - it is bioactive (neurotrophic), structurally complex and highly oxygenated. This video will explain the isolation of this illicium-derived natural product and properties. Two modern syntheses (2019 and 2023) will be discussed, highlighting unique approaches and common methodologies to access this interesting target.
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00:00 Why we should care about illicium natural products
00:47 How it was discovered, isolated and characterized
01:40 The property that makes it exciting¨
02:49 Retrosynthetic analysis and key late-stage disconnections
04:53 Rychnovsky: First total synthesis (racemic) and structural revision
08:29 Kalesse: Asymmetric total synthesis
13:43 Closing remarks
Key references:
- Asymmetric Total Synthesis of Illisimonin A (J. Am. Chem. Soc. 2023, 145, 7021)
- Total Synthesis and Structure Revision of (−)-Illisimonin A, a Neuroprotective Sesquiterpenoid from the Fruits of Illicium simonsii (J. Am. Chem. Soc. 2019, 141, 13295)
- Illisimonin A, a Caged Sesquiterpenoid with a Tricyclo[5.2.1.01,6]decane Skeleton from the Fruits of Illicium simonsii (Org. Lett. 2017, 19, 6160)
- Other related publication: Synthesis of Illisimonin a Skeleton by Intramolecular Diels-Alder Reaction of Ortho-Benzoquinones and Biomimetic Skeletal Rearrangement of Allo-Cedranes (Organics 2021, 2, 306)
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; 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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What do YOU think about the two syntheses? Let me know in the comments!
Massive thank you to all channel supporters! instagram.com/totalsynthesis_official/; www.patreon.com/totalsynthesis
must admit, as a high school student, i barely understood anything yet i found it quite amusing. I'm in awe. chemistry is wonderful.
same lmfao
4 mg, from 96 kg after 10 columns, and then you have to convince the NMR guys to make good 2D spectra... Thank you for putting huge effort into another brilliant video!
I am in awe of chemists
The ingenuity of synthetic chemists never ceases to amaze...
Also doing this work.must be a great test of your resilience and character..just think of the many days and months in the lab when all reactions are failing... can be quite soul destroying.
Oh for sure, few things are worse than trying the same step/ reaction for months without success!
The plants man .. the real chemists. They didn't use any glassware or expensive chemicals 😂
As someone whos doing their bachelors thesis in bioorganic chemistry rn, i’m just in awe… long way to go but wow, if it isn’t worth the ride
Good luck on your thesis 💪
In The Rych-guy's synthesis, the enol ether D-A reaction is actually very interesting! DBU first deprotonates the unsaturated ketone at the delta-position, then the silyl group captures the oxygens. Then a very facile [1,5]-H migration happens before the cycloaddition, so if you deuterates the ketone alpha-H, you will find it in the single bridge in the product. Came across this in a quiz, and missed it
Damn! You outdid yourself again. That second synthesis was insane.
Keep up the good work.
Thanks!
Wow just found this channel, what a phenomenal content! I love it, subscribed instantly :)
Awesome man, thanks!
Great video. That purification process the first group did to obtain the natural product from fruit was insane. It was like comically long. I wouldn't want to be the person to have to do all of that hahah. Very impressive. Not to mention those total syntheses were definitely wild rides. Also very impressive.
Thanks mate! I've literally just published a new video that covers quite some chemistry if you are interested!
Outstanding!
Thank you!!
Amazing video as always ❤
🔥🔥🔥
Great content, thank you.
Thanks!
Always a pleasure. Here's one for the algo
I'm in awe at the patience of this creator.. If you draw out reaction schemes in chem draw, I'm humbled.
I'd predict this molecule class would be toxic with all those epoxides.
I have a degenerative brain disease. It's in it's early stages but scary non the less. This is a huge leap in my opinion. Where do I donate?
These molecules are unfortunately years away from pre-clinical research, let alone clinical! All the best
@@totalsynthesis right but we are thinking in the right direction. If I drop dead right now I could die knowing we are on the right road. This will only be available to the rich for a while but that's why you befriend a good chemist!
How would you synthesize Alstoscholactine and Alstolaxepine?
I would prefer the natural isolation if i was going to ingest🎉
fantastically insightful video as always, quick question do you work in the field of synthetic organic chemistry?
Not anymore!
I hope enzyme chemistry could be used more... so many harsh solvents and reagents.
We may think about how the enzyme in organism that create so much complex molecules with only one stereoisomer they want. That is a good reason that we protect the environment, not to challenge ourselves to acheive the works of the enzymes. All organisms are the master of organic chemist, right?
Maybe I’m being dumb, but should there not be another carbon in the transition state at 5:08? After the diels-alder, the ring on the left seems to be 5 membered, but based on the transition state, it ought to be 4 membered.
Also great video, super interesting!
Yea very well spotted, they lost one carbon in that drawing :)
Interesting video could you please send me a link to the Illusionism A rat study I would like to check out that paper
Illisimonin A: www.sciencedirect.com/org/science/article/abs/pii/S1523706021016321
Jiadifenolide: pubs.acs.org/doi/10.1021/ol9021029
5:37 is it just me or is there an extra carbon coming in out of nowhere for that ring. I’m not too good with organic synthesis but I’m counting more carbons in the diels alder product than there is before the reaction. Am I completely missing something?
Yes, the authors drew the intermediate just prior to the rxn with a carbon less! (just a slip up)
I love organic chemistry and I can't follow literally anything in this retrosynthesis.
😂 I hope the first step was ok?
For the other stepy, I intentionally did not show every detail or talk too much theory so the video doesnt get too long
@@totalsynthesis not your fault at all! And yes, I did see the ester disconnection. But when it went into the ring contraction pinacol rearrangement my head started hurting.
And I thought strychnine synthesis was hard 😂😂😂