8-hydroxyquinoline

[Paregoric Kid]

could 8-hydroxyquinoline be used as the start for an opioid agonist synth?

[pharmboy]

THIS is a question for Robo or Hamilton. Robo __ H .... you out there?

[jonny-5]

or maybe recorcinol

[robojunkie]

Do you mean 8-hydroxy isoquinoline? If so likely yes but ridiculously complicated unless one is aiming for the barebones skeleton of something like levorphanol. The 8-hydroxy isn't going to be all that helpful as is either as this is what would be the 8 position in the morphinan skeleton as well, and this is not usually associated with beneficial activity effects to my knowledge though it would serve as a para-electrophilic aromatic electrophilic substitution activator, which is a good thing were it a 7-hydroxy.

Along these lines, methyl iodide gives the quarternary nitrogen, activating the 1-position, then I imagine some type of benzyl organometallic could be added to the 1, to give a stripped down benzylisoquinoline (precursor to biosynthetic pathway), and if it were a 3-phenolic or 5-phenolic benzyl reagent and a 7-hydroxy IQ, one could perform a bisphenolic oxidative coupling. This would give one the N-methylmorphinan skeleton without the epoxy bridge, though if a 3-OH benzyl reagent was used this could potentially be used to form the epoxy bridge, though I'm not certain of what reagent would be used, I do it can be done. Probably not that hard since the phenolic coupling would rearomatize the "A" ring (the 3-OH ring in morphine) but leave a Michael acceptor (ene-one) at the 5-position for the now 4-hydroxy to add to fairly easily I imagine. It would still have to be isomerized though, the ketone is in the wrong position, as is the other double bond left over. There are ways to do this, easier would be to look up the one of the morphinen TS's. I believe one of them goes through a nearly identical route, or very close at least. Lots of work though for little return, mostly an academic persuit when one could make etorphine from codeine in 5 easy(er) steps.

[pharmboy]

Thanks Robo , but to ME thats a definit No.