Methylation of ephedrine?

ApprenticeCook · DILLIGAF

I got asked an interesting quesiton the other day... Im not into the biological side of things so i decided to ask, ephedrine is not active due to the hydroxyl right? cant cross the blood-brain barrier??? Am i right so far?

So... the question i was asked was... if mdma, with its bridged ether groups is active why could you just methylate the hydroxyl group on ephedrine to allow the molecule to then cross the bbb?

So ephedrine would become --> 1-methoxy-N-methyl-1-phenylpropan-2-amine
This was asked due to the apparent difficulty to use reduction methods due to increasing technology in pill makers to prevent their use... (not that there are heaps of other ways around it but anyway...) but a simple methylation reaction on ephedrine would be rather simple wouldnt it?

I had no idea on the apparent activity of this compound so im putting up for discussion... yes no?

-AC

stratosphere · Mon May 30, 2005 1:23 pm

i believe the compound your discussing would actually be called beta-methoxy ephedrine.
a look through phikal i only came up with one item with a beta methoxy group, BOM the beta methoxy analog of mescaline. shulgrin seems to speculate the potency is roughly equivalent to mescaline although trials were only conducted to the 120mg level with only signs of cns activity.
http://www.erowid.org/library/books_online/pihkal/pihkal017.shtml

by the same logic of crossing the bbb then beta esters of ephedrine might also be worthy of investigation, in the same manner as heroin is more potent then morphine.

loki · guinea pig

esters much easier to make than the methoxyls too... If the changes in activity are similar to the 4-acetoxy dmt's then it will probably mean a higher dose to get the same effect, but at the same time, this might be different if it gets into the brain. I would suspect that in the brain it would have it's main effects on the noradrenalin receptors, being that once it's hydrolysed back to the hydroxy it most closely resembles noradrenalin structurally. It may hydrolyse too readily in the digestive tract or in the blood, which would reduce its effects centrally. it definitely should be studied, but not with a methyl ester (due to the likelihood of it liberating to methanol and being oxidised to formaldehyde)

stratosphere · Mon May 30, 2005 7:13 pm

many esters survive the blood stream unhydrolyized provided there taken intermucosaly or interveniously (e.g. heroin ,cocaine, demerol) , since the pH of blood is 7 this makes sense.

would a simple acid catalyzed ester synthesis work for this?
obviously a strong acylating agent (e.g. acetic anhydride) would acylate the amine rather then the alcohol.

with regards to the methyl ether the only way of doing it thats not more complicated then reducing ephedrine would be acid catalyzed, im not sure how well it would work.