Thank you for these topics. The chemistry of nature, and natural medicines more specifically, was my first love of knowledge. I dig this kind of knowledge 😊
great video really interesting. it's great you split up the topics. as a practicing organic chemists i personally prefer the second half but you do a good job of making even me interested from the beginning, even though it's more biology than i can normally stomach.
Another masterpiece by Total Synthesis! Would love to see a video on the inorganic side of synthetic chemistry - just curious if some synthesis with a story exists :)
At 18:39, why does the Gringard reagent not react with its own ketone group? I don't see why that ketone group would be any less reactive than the ketone of the other fragment, but I am only an undergrad.
Coordination with LiCl prevents Grignard reagent from reaction with its own carbonyl group. You should definitely check out 'turbo Grignard reagents' to learn more about it
I suppose it is more about controlling the temperature. Mg-halogen exchange is relatively facile and can happen under low temperatures, while additions often require higher temperature. If you add the aldehyde to the prepared grignard reagent solution at low temperature and then increase the temperature, the addition will happen at the aldehyde, since an aldehyde is much more electrophilic than a conjugated ketone.
@@seankinney3797 so in this case actually the entire reaction occurs at -78 °C, both halogen exchange and addition "The mixture was stirred at -78 °C for 30 min before it was added a solution of 6 (2.06 g, 10.5 mmol, 1.0 equiv) in PhMe (55 mL) dropwise in 40 minutes at the same temperature." Probably this is: 1) "un-exchanged" ketone is not reactive enough at -78 °C (but the aldehyde is) and 2) once halogen exchange is completed, the ketone of the starting material is much less reactive as it essentially has an alpha-anion. But good question and thinking!
the practice problems on your site were really well written. i like the range of difficulty. make some with all graduate level for the chemist viewers lol
love your videos! just one thing I noticed is why dont you use notation for relative and absolute stereochemistry at 16:44 instead of only absolute and denoting the racemic mixture with text? I know literature also does this but I never understand why or am I missing something?
Great video, you should check out Turkmenistan mint next and its active compound lagochilin, there’s not much literature on it, and it’s such an interesting substance
Is there a preference bias in total synthesis groups where some will be more inclined to do photochemistry, others electrochemistry or high temp reactions based on different lab equipment? Or are most of these labs very similar in setup?
Yes, other research interests definitely bias what reaction types a certain group/professor will leverage. Your average research group will not have the same optionality or sophistication in photo or electrochem compared to e.g., the Baran group. For any given total synthesis, it also depends if it's target-motivated (let's find any way to make molecule X) or methodology-motivated (let's find any molecule that we can make with reaction Y). Some groups do more of the first, while others do more of the second
@@SixTough for top labs, not much will be off limits (you can also get stuff from other groups and departments and improvise). for any generic lab, more things are off limits. one question is also "how niche is your niche application" - e.g., photochemistry, can you use "standard" lamps or do you need really specific ones. same for electrochemistry which is used much less
Think it's the same logic as seen later: the cis-fused ring is like a bowl and with hydrogens pointing top, the bottom face is more crowded (because that's there the other ring and the chain will be at. (my guess)
@@Khalastas That vinyl is also on the top so if it's steric effect would be meaningful, you would assume to see the opposite? See my other response for why. You'd need a really strong molecular model to actually tell where the vinyl would be positioned and what the conformation of that whole chain/ring is.
@ Your guess makes sense to me too. I expect the bicycle and single ring will be twisted rather than flat (with respect to one another), and hence almost overlapping in space. From there, intuition tells me that the lower energy conformation would be with the TBSO-substituted ring twisting into the page due to the the vinyl offering less repulsion than the alcohol. As a result, I think that vinyl tail would end up effectively blocking the bottom face for the addition. The 'bowl' effect of the hydrogens would also contribute in this idea. It would take some modelling, but that's just my intuition - I think it'd be more apparent with a physical model or with those bridging carbon bond angles cleaned up.
Merci beaucoup c'est vrai que si tu n'es pas facile de faire les fameuses fermeture des cycles central des macromolécules et le miel fous je connaissais déjà le rhododendron le la plante et c'est vrai ça donne des hallucinations😮😮😅😅 bravo pour eux d'avoir synthétisé avec il est nucléophile j'en ai déjà utilisé du sel de palladium
@@totalsynthesis you should read this webcomic called homestuck Basically this thing called sollux just gets a seizure cus of some honey and I was so confused but now I think it was mad honey, thankyou great vid :DD
@ there's a webcomic called Homestuck that was really famous a decade ago, and there's a character named Sollux who lives in a house with a bee theme and there's tons of honey everywhere and while i had no idea mad honey existed at the time, the author of the webcomic may have, because there are jokes about Sollux's character that could be references to mad honey, based on his theme
It really doesn't it just gets you fucking munted It does seem to have antibacterial and painkiller effects however - there is an unusual drug called "Labrador tea"
@@MandrakeFernflower Though the plants used in the "original tea" should not be ones that have grayanotoxin: "Generally, Labrador tea is characterized by mild toxicity. All of the species included in this tisane contain sesquiterpenoid ledol, one of the main components of their essential oils. Although low concentrations of ledol in the beverage may have a restorative effect similar to caffeine,1 large doses can affect the central nervous system. Initially, psychomotor stimulation occurs, afterwards seizures and cramps, and eventually paralysis, breathing problems and even death. Another reason for Labrador tea toxicity could be the presence of grayanotoxins (andromedotoxin), cyclic diterpenes with biological activity similar to the Veratrum alkaloids. The symptoms of poisoning include dizziness, hypotension, vomiting, lack of coordination and finally progressive paralysis.32, 34 In humans, there are few lethal poisoning cases, in contrast to livestock (cattle, pets, sheep). Grayanotoxin intoxication is usually related to the consumption of contaminated honey ('mad honey disease'), produced by bees from Rhododendron nectar, or to misidentification of the Labrador species as Kalmia polifolia or Andromeda polifolia - similar but more toxic plants, which can be distinguished by their glabrous leaves and pink flowers (Drugs.com).16, 34 As already stated, R. tomentosum is free from grayanotoxins.35" Source: scijournals.onlinelibrary.wiley.com/doi/10.1002/jsfa.6889
I happened on this site accidentally, I suffer chronic pain, so now addicted to Endone, also I use a sodium channel blocker for irregular heart beat. I am hopeful Suke ....could help.
Thanks for watching! Hope you learned something new or liked it!
Thank you for these topics. The chemistry of nature, and natural medicines more specifically, was my first love of knowledge. I dig this kind of knowledge 😊
great video really interesting. it's great you split up the topics. as a practicing organic chemists i personally prefer the second half but you do a good job of making even me interested from the beginning, even though it's more biology than i can normally stomach.
The synthesis route of Kalmanol was really interesting, particularly the ring closure of the core macrocycle. Great job!
This content is amazing, i love to dive deep. Of course i learn something and i like it a lot.
Thanks for your work 🖖
Thanks, love to hear that!
Another masterpiece by Total Synthesis! Would love to see a video on the inorganic side of synthetic chemistry - just curious if some synthesis with a story exists :)
Thanks! Good suggestion
Ligma
Loved your exercises, I would love to do more of them !
Love to hear, more coming in Feb!
The main reason why we try the synthesis ? The fun bro 😎
It's fun until you get stuck for months haha
.....And someone else is doing all the column chromatography....
@ Nothing worse than doing a large-scale reaction and spending the whole afternoon doing column chromatography
Flex those chemiscles
@supersonictumbleweed sounds bigger than muscules
Great content and in-depth explanations as always !
Thank you!!
good videos first of all
You were fast af
At 18:39, why does the Gringard reagent not react with its own ketone group? I don't see why that ketone group would be any less reactive than the ketone of the other fragment, but I am only an undergrad.
Coordination with LiCl prevents Grignard reagent from reaction with its own carbonyl group. You should definitely check out 'turbo Grignard reagents' to learn more about it
That s indeed a nice question :)
I suppose it is more about controlling the temperature. Mg-halogen exchange is relatively facile and can happen under low temperatures, while additions often require higher temperature. If you add the aldehyde to the prepared grignard reagent solution at low temperature and then increase the temperature, the addition will happen at the aldehyde, since an aldehyde is much more electrophilic than a conjugated ketone.
@ thank you for the explanation!
@@seankinney3797 so in this case actually the entire reaction occurs at -78 °C, both halogen exchange and addition "The mixture was stirred at -78 °C for 30 min before it was added a solution of 6 (2.06 g, 10.5 mmol, 1.0 equiv) in PhMe (55 mL) dropwise in 40 minutes at the same temperature." Probably this is: 1) "un-exchanged" ketone is not reactive enough at -78 °C (but the aldehyde is) and 2) once halogen exchange is completed, the ketone of the starting material is much less reactive as it essentially has an alpha-anion. But good question and thinking!
well researched
the practice problems on your site were really well written. i like the range of difficulty. make some with all graduate level for the chemist viewers lol
Thank you! Will do!
love your videos! just one thing I noticed is why dont you use notation for relative and absolute stereochemistry at 16:44 instead of only absolute and denoting the racemic mixture with text? I know literature also does this but I never understand why or am I missing something?
Great video, you should check out Turkmenistan mint next and its active compound lagochilin, there’s not much literature on it, and it’s such an interesting substance
Thank you. Looks interesting but you werent joking that there is not much literature on it!
Is there a preference bias in total synthesis groups where some will be more inclined to do photochemistry, others electrochemistry or high temp reactions based on different lab equipment? Or are most of these labs very similar in setup?
Yes, other research interests definitely bias what reaction types a certain group/professor will leverage. Your average research group will not have the same optionality or sophistication in photo or electrochem compared to e.g., the Baran group. For any given total synthesis, it also depends if it's target-motivated (let's find any way to make molecule X) or methodology-motivated (let's find any molecule that we can make with reaction Y). Some groups do more of the first, while others do more of the second
@totalsynthesis so most methods are generally not off limits then?
@@SixTough for top labs, not much will be off limits (you can also get stuff from other groups and departments and improvise). for any generic lab, more things are off limits. one question is also "how niche is your niche application" - e.g., photochemistry, can you use "standard" lamps or do you need really specific ones. same for electrochemistry which is used much less
@totalsynthesis and for microwave I guess even more obscure. This is very interesting thank you
One of my favorite accounts
🙏🏻
In the michael addition of the vinyl group (20:12), what explains that it occured from the top face?
I expect it's the hindrance arising due to the vinyl group on the other ring
Think it's the same logic as seen later: the cis-fused ring is like a bowl and with hydrogens pointing top, the bottom face is more crowded (because that's there the other ring and the chain will be at. (my guess)
@@Khalastas That vinyl is also on the top so if it's steric effect would be meaningful, you would assume to see the opposite? See my other response for why. You'd need a really strong molecular model to actually tell where the vinyl would be positioned and what the conformation of that whole chain/ring is.
@ Your guess makes sense to me too. I expect the bicycle and single ring will be twisted rather than flat (with respect to one another), and hence almost overlapping in space. From there, intuition tells me that the lower energy conformation would be with the TBSO-substituted ring twisting into the page due to the the vinyl offering less repulsion than the alcohol. As a result, I think that vinyl tail would end up effectively blocking the bottom face for the addition. The 'bowl' effect of the hydrogens would also contribute in this idea. It would take some modelling, but that's just my intuition - I think it'd be more apparent with a physical model or with those bridging carbon bond angles cleaned up.
Merci beaucoup c'est vrai que si tu n'es pas facile de faire les fameuses fermeture des cycles central des macromolécules et le miel fous je connaissais déjà le rhododendron le la plante et c'est vrai ça donne des hallucinations😮😮😅😅 bravo pour eux d'avoir synthétisé avec il est nucléophile j'en ai déjà utilisé du sel de palladium
Don't use ai images, otherwise bloody good video
Sollux reference?
did hussie know about this stuff before it went viral? he knows a lot of esoteric shit
what's that?
@@totalsynthesis you should read this webcomic called homestuck
Basically this thing called sollux just gets a seizure cus of some honey and I was so confused but now I think it was mad honey, thankyou great vid :DD
@ there's a webcomic called Homestuck that was really famous a decade ago, and there's a character named Sollux who lives in a house with a bee theme and there's tons of honey everywhere and while i had no idea mad honey existed at the time, the author of the webcomic may have, because there are jokes about Sollux's character that could be references to mad honey, based on his theme
If it cures epileptics, why not use it in medicine?
Their claims were cap, it doesnt
It really doesn't it just gets you fucking munted
It does seem to have antibacterial and painkiller effects however - there is an unusual drug called "Labrador tea"
@@MandrakeFernflower Though the plants used in the "original tea" should not be ones that have grayanotoxin:
"Generally, Labrador tea is characterized by mild toxicity. All of the species included in this tisane contain sesquiterpenoid ledol, one of the main components of their essential oils. Although low concentrations of ledol in the beverage may have a restorative effect similar to caffeine,1 large doses can affect the central nervous system. Initially, psychomotor stimulation occurs, afterwards seizures and cramps, and eventually paralysis, breathing problems and even death.
Another reason for Labrador tea toxicity could be the presence of grayanotoxins (andromedotoxin), cyclic diterpenes with biological activity similar to the Veratrum alkaloids. The symptoms of poisoning include dizziness, hypotension, vomiting, lack of coordination and finally progressive paralysis.32, 34 In humans, there are few lethal poisoning cases, in contrast to livestock (cattle, pets, sheep). Grayanotoxin intoxication is usually related to the consumption of contaminated honey ('mad honey disease'), produced by bees from Rhododendron nectar, or to misidentification of the Labrador species as Kalmia polifolia or Andromeda polifolia - similar but more toxic plants, which can be distinguished by their glabrous leaves and pink flowers (Drugs.com).16, 34 As already stated, R. tomentosum is free from grayanotoxins.35"
Source: scijournals.onlinelibrary.wiley.com/doi/10.1002/jsfa.6889
waht
Cringe pun 25:01
It really is like that though
unsubbed for AI trash
Where?
whats the ai?
@@dvdvelde the bears and the thumbnail guy holding the honey!
I happened on this site accidentally, I suffer chronic pain, so now addicted to Endone, also I use a sodium channel blocker for irregular heart beat. I am hopeful Suke ....could help.