Chemiolis - 2024-02-27
Support my channel with patreon: https://www.patreon.com/chemiolis In this video I tell the basics behind Parkinson's disease and the currently used classes of medications. I synthesize a new medication of the MAO-B Inhibitor class, with a different structure compared to medication in the same class, that has recently been developed. This new inhibitor, KDS2010, can reversibly bind to the receptor and is very selective, a combination not found in current known MAO-B inhibitors. It seems to be a lot more effective and is currently in long-term trials.
I get so much dopamine whenever theres a new upload
audio visual catalyst for dopamine synthesis
hilarious fvcking group image. lolol
I'm a retired synthetic organic chemist. I really enjoy watching your videos. Good to see these reactions and the chemistry.
The chipmunk voice on the tongue-twister had me in stitches. Good to see that you're human too. Some people were starting to have doubts.
Really love extensive TLC usage in this video. IMHO most powerful analytical tool available to amateur chemist.
Most powerful and most underutilized. I swear 90% of these chemistry channels are just following a recipe and winding up with "high yields" that are probably a bunch of junk because they haven't done any analytics to confirm. Which is crazy because NMR is relatively new as far as chemistry is concerned, and there are lots of great historic techniques that can give really good insight into chemical identification
@@Spencergolde "so after workup i obtained 250 g of this brown junk which i‘m certain is my product in excellent yield and purity, I have no idea why the follow up reaction didn‘t work though“
I hope someday we cure these degenerative diseases. There's a likelihood that I'm going to get Alzheimer's when I'm older, so it would be nice to avoid that
I hope someday nobody turns sick.
Studying medical chemistry, this hit my spot. Bedankt hiervoor;)
Finding your channel was such a great moment in my life, I'm not a chemistry student or anything, but I've always been interested in chemistry, especially related to psychoactive drugs and medications. The more advanced technical details go over my head, but I always more or less understand what the procedure is about at the end of your videos. You're exactly what I thought NileRed was aspiring to be some years ago, too bad he's now focusing on making extremely long videos about really basic topics (and well, he lacks the sexy voice of yours OwO)
I do agree. Chemi seems to always be working on something extremely captivating with every video. Each molecule he endeavors to synthesize is always outgoing, peculiar, intriguing, and idiosyncratic. I do wish Nile did similar things more often, but to each their own I guess. His voice is also very soothing and attractive, just like you said, while still commanding your attention naturally. I, too, and not nearly as well versed in organic and inorganic chemistry as Chemi is, but I have amassed enough higher-end general knowledge of chemistry through my pyrotechnics and energetic materials discipline to have a huge passion and appreciation for all things chemistry related. He’s definitely top-tier, and I think he is an invaluable asset to the YouTube chemists community.
Oopsie!
And that's how the alien pathogens were released, your honor!
Its really amazing to watch this synthesis, my grandfather was heavily effected by PD and sadly passed away a few years ago, it's really amazing to see the progress in new PD treatment, and it has inspired me to study pharmaceutical chemistry. Love the vid, thank you ❤
You might be interested in looking into Dry Column Vacuum Chromatography (DCVC) for those types of large-scale column purifications. Uses less silica and solvent, but does require a specific type of silica.
I have half-ass tried it before, I have the silica from Merck but I gotta try it again sometime to see how well it really works
DCVC is so overrated, there‘s a reason why it never blew up
You should start a series of such pharmaceutical synthesis.
Excellent video! Parkinson's runs in my family so I'm very glad you brought this to my attention
Always fantastic and so well explained
I love your channel. Always something interesting here.
Love to watch your experiments!
Loved the video! I'm very interested in the clamps you used for your column, they look really useful.
It’s better basics smartrack
@@Chemiolis It looks super nice, but it's also relatively expensive. 600-1000 bucks for some folded aluminum and polymers for a single workspace is quite excessive…
Building something comparably sturdy, yet cheaper with some extruded aluminium profiles (I-type / with T-slot) from the hardware store should be a nice side project.
That’s really impressive medicinal chemistry 👏🏼
Very nice video!
The amount of celite is horrifying! such an amount will make a pretty wide band of mix on silica with decreased separation :/
As it is lab scale, it could be beneficial to use other methods (silica pad only to cut out tar and most Pd, bisulfite adduct for aldehyde purification and just protonating amine, to separate it from non-basic stuff in the mix),
Love TLCs! <3 But it would be a great idea to use more specific stains, like bradys reagent one for aldehydes/ketones and amine specific (Nihydrin). Never forget about UV (all compounds are aromatic, so it would be ideal) and I₂ vapors (also great for aromatic ones).
And as always: Wonderful video!
I'm enjoying your video. I hope, one day, you will have a video about blood pressure-lowering drugs, similar to Lisinipril.
Keep doing what you're doing.
Gotta love how Selegiline is just propargylated meth
This is really interesting to see! Where do you find the information for these videos?
Is this about ariadne? I've been fascinated by this since seeing it in PIKAL and listening to the Mike Cunningham interview on Hamilton Morris's podcast!
This (not new) drug made waves in PD research in the 2020-22 year range. According to Neurobiogen's own website, they have yet to get an accepted publication on its efficacy in a PD model. Wierdly enough, it has gained more attention as of 2023 as a "wonder drug" for weight loss/dieting. This makes me suspect that there are issues with side effects at play, but that's only speculation. Anyway, great video as always!
Direct and indirect dopamine agonism (i.e. by limiting its breakdown) is accompanied with nausea. This wouldn't be the first dopaminergic substance marketed for weight loss.
@@Psychx_ That makes sense. I guess what I meant more directly was/wanted to know was: why is this drug's PD relevance seemingly overshadowed by its prospect as a diet pill?
@@qcard76 Because creating a single new drug literally costs billions of USD and failure can happen very late in the development process - even during phase III studies, which are the last hurdle before approval.
It's pretty standard practice to see if a substance can be salvaged to treat another condition if it fails to reach its primary goals but has an otherwise favorable pharmacologic profile (i.e. good resorption, med-long duration of effects, predictable elimination, large therapeutic window, low toxicity).
The most prominent example for such practices are otc sleeping pills containing Benadryl/Diphenhydramine. That substance was developed to treat allergies, and making people sleepy was a side effect.
Nowadays, there are antihistamines that don't cause tiredness anymore and Diphenhydramine is sold as a sleeping aid.
The nausea medicine Metoclopramide is a low-potency antipsychotic btw. and Thalidomide (Contergan) is now used for treating lepropsy, certain cancers and Crohn's disease…
Im not too thrilled about about someone trying to repurpose anything into a diet drug so quickly, and even less thrilled when something is called a wonder drug.
But if it affects how you interact with dopamine, it can have the potential for treating some causes of weight gain.
Love the neurobiological background. Find it interesting that some antipsychotic medication, being dopamine and serotonin receptor antagonists can apparently cause parkinson's like symptoms in high doses.
On the topic of serotonin-receptors are you interested in synthesizing some migraine medication like tryptans in the future? ;)
I'll try it
Was the sodium carbonate decently priced as well?
Hi Chemiolis, can you synthesize Dual donor-acceptor covalent organic frameworks for hydrogen peroxide photosynthesis as in 10.1038/s41467-023-40991-7 and and demonstrate the production of hydrogen peroxide in sunlight?
The time to use that fancy reductant has come!
when new video?
Where did you get your stone heating mantle
Fantastic, i was facsinated by the use of the 1-hydrosilatrane, the endind got me, what a way to lose the product haha
Finally some TLCs
As for antiparkinson medications, i always thought amantadine was really interesting. Just for how "simple" it is, a little fragment of diamond (essentially) with an amine stuck on there.
I clicked on this video thinking you were gonna make that one Parkinson's-inducing chemical
hi ! i used also AcOH glacial and NaBH4 to form a milder reduction agent (AcO)3BHNa , it worked for reductive amination really well , something like 78% yield
Yeah, STABH has very similar reactivity to cyanoborohydride, but it’s a bit more mild. Works well for a lot of reductive animations/alkylations. For people like us who can’t easily get cyanoborohydride (or those who don’t want to work with it) STABH is almost perfect due to its ease of preparation prior to a reduction. The problem with STABH is its extreme sensitivity to water, and protic solvents which limits the solvents that can be used to DCE, DCM, THF, dioxane, toluene, etc. The reactions between STABH, IPA, and EtOH are slower; however, reductions with STABH tend to take long periods of time.
Out of curiosity, what solvent did you use, and how long did you run the reaction?
On another note, sodium monoacetoxyborohydride is apparently able to reduce nitriles and amides to amines which is interesting. Also, there’s a book that has a bunch of info on the capabilities of reducing agents called “Handbook of Reagents for Organic Synthesis: Oxidizing and Reducing Agents.” I highly recommend it.
i clicked on this video and i was already liked.
Your reductive amination mightve not worked because you did not allow time to form the imine. You also need a drop or two of acetic acid to help this along. It's possible your reductant just reduced the aldehyde to the alchol. This is why a weaker reductant is usually used (ie NaCNBH3 over NaBH4)
You should try Potassium permanganate as a stain, dip it in and done (wait a bit or heat the plate to 250 °C until you can see the stuff :D)
You say you lost your final product yield from the reagent change but the TLC looks pretty good with product being by far the strongest spot and no starting material, any chance you just lost lots in the workup?
I don't mean this to sound negative, love the videos
Two questions, would palladium on carbon work as a catalyst? (Ie is there a specific need to use Pd(PPh3)4?) second, did you recover the catalyze afterwards?
I'm not an expert by any means, but as far as I know a ligated palladadium catalyst (Pd II+) is commonly used as the reactive species for this kind of coupling reaction.
Pd/C is generally used for hydrogenations, whereas the Ligands of the Palladium Complex can be specifically tuned for improved reactivity/ selectivity on
coupling reactions regarding substrates/educts (and stereochemistry).
Pd/C can be used as a coupling catalyst (like a Suzuki coupling in the video, or for Stille coupling) it might be less efficent, or you would need a co-catalyst
Hope this helps, further information might be in the literature links at https://en.wikipedia.org/wiki/Palladium_on_carbon
@@moritzwebers7986thanks, it makes sense ig it would be much less efficient since pd/c is better fo rhydrogenations
There are some Suzuki couplings that have been done with palladium on carbon
Is it a prodrug?
Ah good old Suzuki coupling. So many flasks broke in our lab course while degassing with freeze-pump-thaw.
Also, judging by the mucus colour, your solution was not quite degassed. Git gud >:) Should stay a nice pale yellow after adding in the tetrakis.
May explain the side products though
Why go for Pd(PPh3)4, when Pd XPhos G3 is the same price per mole with much higher performance?
Pd(PPh3)4 has a molecular weight of 1155.56 g/mol, while Pd XPhos G3 has 846.45 g/mol. 1 g of the former costs about 50€ on Sigma Aldrich, or 12,50€ for 250 mg, while the latter costs 80€ on sigma. Xphos pd 3 is way more expensive, the difference of molecular weight is only like 73%. Using xphos pd g3 would be a waste even if you could theoretically use less catalyst because he doesn‘t do proper synthesis under inert conditions
does this mean i should lay off my regular use of 500mg+ diphenhydramine (i dont have pd)?
No.
The regular use of diphenhydramine has been linked to dementia. So yeah, you might want to quit if you don’t want dementia. On the other hand, I’m not your mother so you don’t have to listen to me.
My cynicism is thinking they found a molecule that causes PD while it treats it.
I wonder why THC has such a positive effect on the tremors and motor functions of people with PD
THC increases dopamine in your brain
What the hell was that catalyst at the beginning of the synthesis???
Pd(PPh3)3 ?
a very common one in palladium coupling reactions
@@josefanon8504still looks wild though
@aidange8863 @josefanon8504 it‘s Pd(PPh3)4. very easy to make
@@user-zo2ie1ml2d
oh thanks, don't know how I made that mistake.
like breaking a key off in a lock
Hate using Pd(PPh3)4 due to the TPPO impurity’s formed 😂 Pd(dppf)Cl2 is much better and is more stable
what do you mean with TPPO?
triphenylphosphine oxide@@EbbeLoos
@@EbbeLoos triphenylphosphine oxide
thanks:)@@chemistrycapital
@LtLolcopter - 2024-02-27
I really enjoy these types of videos where they synthesis actual medications. I find it fascinating.
@mnxs - 2024-02-27
*synthesise/synthesize 🙂
But yes, it's super fascinating!
@markdombrovan8849 - 2024-02-27
*he
@thomasgarbe8354 - 2024-02-27
"Medication" is a euphemism. In fact, this artificial tri-fluoridated chemical I do not expect to benefit anyone.
@markdombrovan8849 - 2024-02-27
@@thomasgarbe8354 that's okay, you are not a medical professional anyway so your opinion on this is irrelevant
@mnxs - 2024-02-27
@@markdombrovan8849 OP did say "these types of videos", ostensibly referring to multiple channels' creations. Thus, 'they' is appropriate, since there are different creators.