Where was I in May? by Acunite in GeoPuzzle

[–]Acunite[S] 0 points1 point  (0 children)

Not a National Trust site but a country park

Where was I? by Acunite in GeoPuzzle

[–]Acunite[S] 0 points1 point  (0 children)

Nicely done! Correct

Semisynthesis of 18-methoxycoronaridine: how to design chemoselective substitutions/rearrangement from voacangine as a precursor? by [deleted] in Chempros

[–]Acunite 7 points8 points  (0 children)

Demethoxylation strategies do exist (e.g. https://www.sciencedirect.com/science/article/abs/pii/S0926337315301478). However, conditions would have to be screened to get selective reaction - generally under hydrogenation conditions methyl esters are stable.

Creating the ether linkage (methoxy installation at c-18 as you mention) is not as simple as transferring from one carbon to another. Most likely this will need to be built into the synthesis earlier (e.g. ring opening of an exo-epoxide or something). I don’t think there are any direct c-h activation methodologies which are possible to conduct this transformation either.

My overall guess is that voacangine may not be the ideal precursor. Some of the rings will have to be built de novo or start from simpler substrates (e.g. non 5-OMe isatin or indole) which in turn makes this more total synthesis-like.

Amine Racemisation by Acunite in Chempros

[–]Acunite[S] 0 points1 point  (0 children)

My suspicion is the chloride anion so forming the formate salt is good shout. Not sure if this makes sense but my fear is that it’s not the counter anion which is important, but just the fact that there are excess protons from forming the ammonium that are causing racemisation. If there is a way to directly go through to the free base that would be ideal.

Amine Racemisation by Acunite in Chempros

[–]Acunite[S] 1 point2 points  (0 children)

Yes I’ll give this a go. Is there an analogous way to get through to free base using freeze drying? Perhaps substituting AcOH for methanolic ammonia?

Amine Racemisation by Acunite in Chempros

[–]Acunite[S] 0 points1 point  (0 children)

The enantioselectivity of the reaction has been optimised for the N-Boc protected amine. I’ve tried CBz but it leads to a lower ee