3,6-diisopropionylmorphine/6-iPM/propionylisopropionylmorphine?

[Limpet_Chicken]

Whilst I'd say that yes the dipropionyl ester homolog of diamorphine has been sufficiently characterized for it to be decently known, I can
find NOTHING on changing one or both ester moieties for isopropionyl. Are any permutations known such as 3,6-diisopropionylmorphine, 6-monoisopropionylmorphine or propiony/-isopropionyl heterogenous esters of morphine known at all?

Is the isopropyl group (potency dramatically starts to drop off extending from a 3- to a 4-carbon chain for the ester groups, having tried n-butyrylmorphine and it being found wanting in terms of potency so really there aren't any other secondary alcohol esters other than maybe isopropenyl or much room for tweaking there, bar straight chain propynyl or halogenated derivatives (possibly unsuitable for injection in the case of halogenated esters possessing a multiple bond (thinking of ethchlorvynol here which if injected causes potentially severe lung damage for some reason)


But particularly in the case of mono/diisopropionyl esters or propionyl-isopropionyl diester of morphine what is known, to compare it to dpropionylmorphine (one of my all time favourite opioids, for its LONG duration of action, its damn potent kick (perhaps as strong again as heroin as H is to morphine and its being euphoric as hell when IV'ed or IM'ed/SC'ed)

I presume these MUST have been tested by big pharma when opioid development of morphine esters was being undertaken, since prope dope was, surely diisopropionyl/propionyl-isopropionyl esters must have been tested for duration, potencyl, abuse potential?

Do the isopropionyl esters retain the potency of n-propionyl, and the extreme lengthening of duration to more than double?

 

[sekio]

Isoproprionyl isn't valid nomenclature, you can't have isopropanoic acid, the carboxylic acid needs to be on a terminal carebon and can't be on a secondary. 2-carboxypropane is actually isobutytric acid.

 

[Limpet_Chicken]

Well thanks. Nomenclature aside, anybody have experience of isobutyrylmorphine esters? I've tried di-n-butyrylmorphine and it was nothing special.

Although what I meant was not addition of a carbon to the isopropyl group, but where isopropanol has R-OH, oxidizing to C-OOH, taking the 2' carbon of isopropanol as the terminal carbon. And (hypothetically) oxidation if a method suited to oxidation of alcohols to carboxylic acids were used, one would then have 2-propanoic acid, no? and then if an acid halide were produced from same, addition to an alcohol or phenol would result in the formation of an isopropyl ester would it not? (this is about working out nomenclature rather than synth discussion btw).

In any case..isopropionyl esters, I find some reference to them online. Such as fr.ex reference to isopropionyl esters of propionic acid.

Has anyone here tried di- or monoisobutyrylmorphine? I've tried n-butyryl and it stank. In both senses of the term. Working with n-butyric anhydride is never pleasant, stinks like sick from the butyric acid released on hydrolysis. That awful stink hung around for days, weeks if you count use of the DIY vac chamber (basically two inch-thick plexiglass outer sheets over a rubber O-ring mounted in a meter of steel pipe about a meter long with a 6-7 inch ID and a vac barb and pressure gauge, screwed into a tapped hole and wrapped in teflon tape. Second-hand Single stage rotary vane pump would evacuate down to -30something inches Hg, closer to 40. in less than a minute, so not bad for a DIY job) and used to vac-dessicate the product over KOH resulted in both the chamber and any use of the pump fouling the air up for days as traces of butyric acid were vomited forth

 

[Bagseed]

bulkier substituents probably slow down hydrolysis due to steric hindrance... if the butanoic acid ester wasn't interesting, there is a good chance that the isobutanoic one won't be good either...

 

[sekio]

In any case..isopropionyl esters, I find some reference to them online. Such as fr.ex reference to isopropionyl esters of propionic acid.

That's isopropyl, not ioqproprionyl.

 

[Bagseed]

and isopropyl ethers might be crap, see codeine (methyl ether). ethers are much harder to metabolize, hence the low potency of codeine.

 

[Limpet_Chicken]

Yeah as a terminal 3 or 6' substituent on morphine as sidechain certainly, an ether isn't going to help anything, that'd turn morphine analogs into codeine ones.

Would be curious to taste-test 6-propionylcodeine analog, but not enough to sacrifice any of my morphine to create some! hell no. I can't afford to piss it down the drain. Although the n-propionyl diester of morphine has to be the best morphine ester I've ever had. Would love to make some of the dipropionyl or 6-monopropionyl dihydromorphine esters some day. Knowing what an arse-kicking the 6-monoacetyl ester of dihydromorphine packs. I've been badly wanting to try desomorphine-D (via a clean route, catalytic H2 etc for reduction of the intermediate not that ugly as fuck krokodil clusterfuck the russki suicide-addicts make via phosphorus-iodine reductions.) to see which of the two has the most intense rush. I've heard some pretty crazy things about desomorphine regarding the legendary rush on IV (in forms not custom-made to rot the flesh off people's bones and produce the closest thing to a zombie movie your ever likely never to want to see of course)

Never got further than alpha-chloromorphide though, for the sole reason that I decided to bioassay that intermediate itself, with MOST perculiar results (not even close to opiate-like, rather, subjectively pure psychostimulant but not akin to DARIs or amphetamines or other such releasers of monoamines. Weird, unique kind of stimulation, comparable only with some crappy kratom I once got sent as by accident, several kg for nothing from a herb store that I never ordered or was charged for, old stuff, not strong in opiate-like effects but comparable in some sense to the weird ass stimulant effects of the chloromorphide.

I got sidetracked big time, waylayed, and jumped on the highway towards desomorphine before reduction to it of the intermediate in question (will leave it at that rather than go into details synthetically), pharmacologically it was just too different, too strange to ignore. It did relieve withdrawal, to a degree although not with the same efficiency as say a shot of morphine would do, but thats the only way I could detect any opioid activity, otherwise it was ALL about this weird ass psychostimulant effects, and I strongly suspect, would have been convulsant had I pushed the dose higher than my scaling up trials eventually peaked out at, as clonus and twitching of the extreities began to occur at the maximum doses tested. Weird shit. Not unpleasant, just outright strange. I'd LOVE to know exactly where the stuff binds in the CNS. Suspicion is DOR agonism perhaps. Or perhaps like thebaine, strychnine-sensitive glycinergic receptor antagonism, although it didn't FEEL like the stimulation from pod tea or other thebaine-containing opioid mixtures or isolates. Unfortunately I've tried neither low-dose strychnine/brucine, nor have I tried subtype selective agonist ligands for delta-1 or delta-2, or mixed DOR 1/2 agonist opioids without MOR agonism to cloud the waters of perception. my fault for being such an insatiably curious little bugger

 

[Limpet_Chicken]

And oops, didn't mean to say isopropionyl ester of propionic acid. MEANT to write 'isopropionyl ester of n-propanol and vice versa'