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Author: Subject: Stereochemistry of the ibogaloid catharanthine
Monoamine
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[*] posted on 12-10-2021 at 13:30
Stereochemistry of the ibogaloid catharanthine


I got interest in catharanthine, since the non aromatic pi bond should allow for some interesting chemistry and unlike the more well-known ibogaloids, the indole ring isn't substituted yet.

But when research it a bit, I found several inconsistencies in its stereochemistry. This is how Cayman chemicals shows it:

But this is how Clearsynth shows it:

The one by shown by Cayman is much more consistent with other ibogloids. So I'm wondering if anyone has some insight as to which one is correct?

Ot maybe I just not understand stereochemistry, lol.


Cearsynth.png - 91kB

Caymen.png - 80kB
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Tsjerk
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[*] posted on 12-10-2021 at 13:37


The first doesn't show stereochemistry, only the lines that are darker (broader) show a group is pointing towards the viewer, dashed lines point away from the viewer

[Edited on 12-10-2021 by Tsjerk]
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draculic acid69
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[*] posted on 13-10-2021 at 00:00


Quote: Originally posted by Tsjerk  
The first doesn't show stereochemistry, only the lines that are darker (broader) show a group is pointing towards the viewer, dashed lines point away from the viewer

[Edited on 12-10-2021 by Tsjerk]


I didn't know this until now.now I know.
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Monoamine
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[*] posted on 13-10-2021 at 15:28


Ah got it. Thanks. I guess what confused me is that in clearsynth picture the methyl bridge from the basic nitrogen to the cyclohexene ring is drawn as if it is in the front, not in the back.

But then again, I've also never seen a hydrogen atom with four bonds to it before lol.
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[*] posted on 13-10-2021 at 19:47


Quote: Originally posted by Monoamine  
Ah got it. Thanks. I guess what confused me is that in clearsynth picture the methyl bridge from the basic nitrogen to the cyclohexene ring is drawn as if it is in the front, not in the back.
Yeah, the bridge is drawn in the front, but also if you compare the two structures, you can see that the whole molecule is flipped relative to the Cayman structure. So in the Clearsynth structure you’re looking at the molecule from the “back,” relative to the way Cayman shows it, thus the bridge is shown in the front, and the carboxylic acid would be pointing back had they shown the stereochemistry there.

If you have a model kit, try building a 3D model of the molecule and rotating it around to look at it from different perspectives. You should be able to see that both versions are accurate depictions.




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[*] posted on 14-10-2021 at 09:53


Thank you for opening this can of worms!

There seems to be confusion over the stereochemistry on wikipedia too. The page on catharanthine shows the cage behind (with indole to the left). Ibogaine and related alkaloids have the cage in front. But on the Vinka alkaloids page, the cage of catharanthine is shown in front.

I think catharanthine is interesting as a possible precursor to ibogamine, provided it shares the same stereochemistry, which I think it does. Since catharanthine is already a precursor to vinblastine for cancer treatment, it should enjoy commercial supply that ibogamine lacks. The best price I could find after a quick search was $210/g, but it is also prominently mentioned as an alkaloid in Madagascar Periwinkle (Catharanthus roseus). Does anyone have better leads on this compound?
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[*] posted on 10-12-2021 at 16:27


After more investigation, I've found that (+)-catharanthine does indeed have the opposite stereochemistry of the alkaloids derived from iboga, which is disappointing. I also learned that, even if the stereochemistry had been suitable, it would not be straight forward to convert it into coronaridine or ibogamine because hydrogenation would tend to come from above the structure shown, forcing the ethyl group down, not up as shown in coronaridine here:

catharanthine.png - 5kB Coronaridine.png - 4kB

Removing the ester first might help, except that the transition state essential to the decarboxylation is too strained to proceed, as it would for coronaridine, due to the double bond within the ring. So the double bond has to be moved first:

decarboxylation_mechanism_121021.JPG - 39kB

The bottom line, though, is that catharanthine is a dead end for access to iboga alkaloids because of its stereochemistry.

The sequence is from Scheme 11 of Strategies and Tactics in Organic Synthesis edited by Michael Harmata, found on Google Books.

[Edited on 11-12-2021 by Jenks]
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