tetrahydrodesomorphine-D

[Limpet_Chicken]

Whilst desomorphine is well enough known, tetrahydrodesoxymorphine-D, is much less common.

However, whilst desomorphine-D itself can be created by catalytic hydrogenation of the precursor to make it, using palladium catalysts, (wont go into synth routes, just the very very end reagent used is important for other reasons in this case. The rest of the process is unimportant for the purposes of this thread. The catalyst however, is salient in this case)

Palladium on the precursor it needs to be used on, in various guises results in desomorphine. However if the more powerfully active platinum catalysts be used on the same compound that the plad cats would be used on for desomorphine, such as colloidal platinum, Pt oxide or plat cat, then the result is tetrahydrodesoxymorphine-D.

Is it active? how long acting is it compared to desomorphine-D? better rush, lesser one? if its active, what is the general dose range in a nontolerant subject (again, as in previous threads, this is asked to derive a baseline for potency figure, the end user, should it be active, is HIGHLY opioid tolerant.
How fast is the onset? desomorphine-D itself is very quick to act when given intravenously is it not? Should think so because of the rush it is known for.

 

[sekio]

AFAICT, tetrahydrodesoxymorphine = the epoxide ring hydrogenolized to an alcohol. Like so.

It pretty much ruins activity - "greatly decreases" I recall reading. Hence you don't see a lot of these type of cmpds.

It is incorrect to call it tetrahydrodesomorphine D. The alphabetical suffix is actually used to differentiate the various positional isomers of dihydrodesoxymorphine which result from elimination of hydrohalic acids from [radio static interfering with rest of synth discussion ]. Desomorphine we all know and love is actually "dihydrodesoxymorphine D" I believe - at least one of the compounds sports a free phenol as tetrahydrodesomorphine does, and others (desomorphine C) resulting from electrolytic reduction of [static] have unsaturation/double bonds in them.

More can be found by scouring the early literature... here's a review with a neat table on comparative opioid pharmacology.

 

[Limpet_Chicken]

I meant the compound retaining the epoxy bridge but having the A-ring (I mean the one at the far north, in the above drawing) fully reduced to a cyclohexane.

 

[sekio]

That would be (let me count here!) octahydro-desoxymorphine? perhydro-desoxymorphine? I'm pretty sure you need the aromatic ring for opioid effects: see also the "morphine rule".

There is no record of such a compound on Reaxys, so that's a bad sign.

Two other things; you'd introduce three, possibly four new chiral centers (shown with asterisks), and of course hydrogenation of aromatic rings is "working uphill" thermodynamically speaking, and not something that is doable without crazy high pressures.

Before you ask, perhydro-levorphanol is also unknown (same cmpd as above minus the epoxy oxygen)

 

[serotonin2A]

The aromatic ring is required for binding with reasonable affinity. There are certainly other structural modifications that could be made to offset the lack of an aromatic ring (eg, addition of an N-phenethyl group), but why bother?

 

[Limpet_Chicken]

Have you any specific data on N-phenethyl, or perhaps N-cinnamoyltetrahydrodesoxymorphine-D? is N-phenethyllevorphanol or N-cinnamoyllevorphanol known?

Why bother? Why BOTHER? good fucking god WHY? lol I haven't laughed so hard since waking up today. Why bother indeed. Lmao.

 

[serotonin2A]

Have you any specific data on N-phenethyl, or perhaps N-cinnamoyltetrahydrodesoxymorphine-D? is N-phenethyllevorphanol or N-cinnamoyllevorphanol known?

Why bother? Why BOTHER? good fucking god WHY? lol I haven't laughed so hard since waking up today. Why bother indeed. Lmao.

I'm sure you are familiar with known opiate SAR and the morphine rule, which these analogs would violate. There are certainly exceptions to SAR, but it is going to take more than just laughter to convince anyone knowledgeable about MOR pharmacology that this is likely to be a useful synthetic direction.

If you reduce the potency of morphine 100-fold by removing the aromatic ring, and then try to compensate for that by adding an N-phenethyl group (or maybe even trying to make an etorphine analog) to mitigate the potency loss as much as possible, you are going to be left with something that likely isn't nearly as active as your starting product. So yes, why bother?

 

[Limpet_Chicken]

Unless totally inactive then I like to investigate and explore.

I apologise if I caused any offense BTW, it was not my intent. I was not laughing at YOU, but rather, at the idea itself, that such was not worth investigating. If I did offend then I appologise, and whilst I do not think it excuses me if I did so, its been a long and horrible day. Some of the longest myoclonic/atonic seizures I've ever had the shite luck to have and I am still pretty scrambled (doesn't help in that particular respect that I've only just come out of another one.) so, currently no, I'm not what you could call knowledgeable in most respects, in anything. I doubt I could cook dinner right now, never mind opioids. Not with this level of post-ictal shitty.

Etorphine analogs are off the menu, I do not live alone, so it would be unfair and wrong of me even to try. My own tolerance, for that matter would prove little protection against an accident, and furthermore, there would be nobody who could partner me in the lab anyhow, let alone doing something like that. About 70-80x morphine is the most I'd dare go. Fentanyl (vailla edition that is) would be the most if the compound were exceptional, but I'd not attempt synthesis of fentanyl itself because I just don't care for it in the first place, and nor do I want to massively blow up my tolerance. Its already too damned large. As soon as I either manage to get my doc to finally give me the go ahead for a memantine script, or order some, then some naltrexone is going to get ordered so as to drop it down.

Right now however...I think my brain just took a bath in boiling perchloric acid. and somebody must have opened up my iodine and poured the bloody lot all over my cerebral cortex after cutting open the top of my head,