Differences Between Dihydrodesoxymorphine C and D

[G_Chem]

I’m really curious if there’s any information regarding any pharmacological differences between these two compounds? I’m finding very little on the subject.

Edit- I’m sorry that’s Desoxymorphine C and Dihydrodesoxymorphine D..

Thanks

-GC

 

[sekio]

ref- d7-desoxymorphine - "the LD50 is 90, the analgesic dose is 0.2, the onset of effect is very rapid (about five minutes), and the duration of effect is short (about 53 minutes). The comparable values for morphine are LD50 539; analgesic dose, 1.70; onset of effect, 15 minutes; and duration of effect, 144 minutes." Presumably those are mg/kg in rats?

there's also a JPET journal article that provides info on the two others. I can infer from the abstract that desomorphine is the most potent, least convulsant and widest therapeutic index, compared to its unsaturated friends. I'd still expect desoxymorphine-C to be a potent narcotic though. Likely about as potent as desomorphine.

 

[Nagelfar]

I have a double -take to note: 'desoxymorphine' then "desomorphine"

Reminds me of that 'heroin #3', 'heroin #4'. Though this is a little more in-depth, the four and five designations (base and HCl) seemed mainly there for nonchemists

 

[G_Chem]

This may be a stupid question for all I know, but is it possible to have the acetyl (or any..) ester of desomorphine?

After reading through the few experience reports I could find on Desomorphine it sounds like a cross between dihydromorphine, oxy and hydromorphone.

-GC

 

[sekio]

This may be a stupid question for all I know, but is it possible to have the acetyl (or any..) ester of desomorphine?

Yes indeed, I don't see why not. If you are familiar with the line drawings used to denote chemical structures, presence of "OH" or "HO" groups are sometimes indicative of an alcohol group. (as long as some exceptions are excluded, like carboxylic acids or peroxy compounds) Those are the locations that acetate groups are attached onto, increasing fat solubility & therefore potency). Desomorphine has one of these, at the 3-position, attached to the topmost phenyl ring.

(4R,4aR,7aS,12bS)-3-methyl-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl acetate would be the IUPAC name. Just rolls right off the tongue,

I do not know whether this compound would pose any benefits over "normal" desomorphine. Heroin is useful because morphine is a bit of a poorly behaved drug, by switching to the ester you produce a more potent compound that can be given orally in smaller doses than morphine would need.

Usually, the phenolic 3-position hydroxy is required to be present and capable of hydrogen bonding to produce agonist activity at opioid receptors. This is why codiene and ethylmorphine (3-O-methoxy / 3-O-ethoxy morphine) is much less effective than morphine, yet heterocodeine (6-O-methoxymorphine) that has the methyl group moved to the other alcohol is more potent than morphine!

Also, even though it is known that heroin produces strong narcotic effects, it is known that purified heroin is actually not very good at binding to the opioid receptors in the absence of esterase enzymes which would cleave the acetate esters. (nor is 3-O-acetylmorphine) It just so happens that your body will remove tbe 3-O-acetate basically instantly, so the effects of heroin are actually more correctly said to be from 6-monoacetylmorphine and morphine.

 

[G_Chem]

Yes indeed, I don't see why not. If you are familiar with the line drawings used to denote chemical structures, presence of "OH" or "HO" groups are sometimes indicative of an alcohol group. (as long as some exceptions are excluded, like carboxylic acids or peroxy compounds) Those are the locations that acetate groups are attached onto, increasing fat solubility & therefore potency). Desomorphine has one of these, at the 3-position, attached to the topmost phenyl ring.

(4R,4aR,7aS,12bS)-3-methyl-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl acetate would be the IUPAC name. Just rolls right off the tongue,

I do not know whether this compound would pose any benefits over "normal" desomorphine. Heroin is useful because morphine is a bit of a poorly behaved drug, by switching to the ester you produce a more potent compound that can be given orally in smaller doses than morphine would need.

Usually, the phenolic 3-position hydroxy is required to be present and capable of hydrogen bonding to produce agonist activity at opioid receptors. This is why codiene and ethylmorphine (3-O-methoxy / 3-O-ethoxy morphine) is much less effective than morphine, yet heterocodeine (6-O-methoxymorphine) that has the methyl group moved to the other alcohol is more potent than morphine!

Also, even though it is known that heroin produces strong narcotic effects, it is known that purified heroin is actually not very good at binding to the opioid receptors in the absence of esterase enzymes which would cleave the acetate esters. (nor is 3-O-acetylmorphine) It just so happens that your body will remove tbe 3-O-acetate basically instantly, so the effects of heroin are actually more correctly said to be from 6-monoacetylmorphine and morphine.

Yea based on my reading it seems as though Dihydrodesoxymorphine doesn’t deal with the same bioavailability problems that morphine does.

So if the acetyl attaches at the 3 would that mean it’s possible to be less active if we extrapolate from 3-MAM and it’s relative lack of activity? And would this be a similar situation to when I asked about acetylhydromorphone which also attaches at the 3?

-GC

 

[sekio]

So if the acetyl attaches at the 3 would that mean it’s possible to be less active if we extrapolate from 3-MAM and it’s relative lack of activity? And would this be a similar situation to when I asked about acetylhydromorphone which also attaches at the 3?

Depends on your assay method. Looking at the binding affinity of the pure compound might give a false idea that it's somehow weak, but anyone who knows a thing or two about heroin/thabacon/other morphine esters will probably be able to guess that it acts as a prodrug for desomorphine. It could concievably increase potency as a painkiller/euphoriant when given to a living animal. Worst case it's slightly less effective than desomorphine by weight.

 

[clubcard]

I think krokodil actually contains some or is ALL desoxymorphine-C (deoxymorphine-C as Bentley named it). DOI: 10.1134/S1061934808040096 I don't know if the shape of that C ring is important when their is no group at 6. Both compounds are very lipophilic and have a higher LogP than morphine (for example). I THINK that the Diels-Alder abducts of this class have been explored and, in short, they aren't particularly exciting.

It seems to be turning up in many nations. It looks grim. I would go the extra mile and form the calcium salt so the phenolic products can be isolated and even then, it does not look good.

I mean, the simplicity of the synthesis must seem attractive but it seems like a long walk off a short pier. I do not think that the RP isn't required and HI + H3BO3 will work fine BUT if you are heating RP & I2, do bear in mind that PI3 & PH3 are formed. I've seen some really sad stories in which people sussed out that HI could be produced from RP & I but they were venting the reaction into the room and it did not end well. Just because a reagent is freely available in your part of the world does not mean that it's safe.

 

[G_Chem]

Well honestly the typical krokodil route going from codeine sounds nasty, low yielding, and overall more work than it’s worth.

That said chlorination of morphine followed by palladium hydrogenation doesn’t sound bad.

-GC

 

[clubcard]

Well honestly the typical krokodil route going from codeine sounds nasty, low yielding, and overall more work than it’s worth.

That said chlorination of morphine followed by palladium hydrogenation doesn’t sound bad.

-GC

But this is being 'cooked' in peoples homes using easily acquired precursors and a route that can be carried out in syringes. They cannot afford hydrogenation units let alone catalysts. It is a drug of the poor, not for those people blessed with training in chemistry or $5000/month to buy the stuff.

 

[G_Chem]

But this is being 'cooked' in peoples homes using easily acquired precursors and a route that can be carried out in syringes. They cannot afford hydrogenation units let alone catalysts. It is a drug of the poor, not for those people blessed with training in chemistry or $5000/month to buy the stuff.

I’m not talking about poor folks synthesizing krokodil, and palladium hydrogenation (at least in this context, obviously other synthesis need high pressures) does not need high pressures a simple hydrogen atmosphere with a balloon on top will do. Good agitation necessary of course. Also the catalyst isn’t all that expensive and completely reusable, and very easy to recover...

I base that on the fact morphine and esters of morphine can be hydrogenated to their dihydro counterparts with very little pressure, so long as a hydrogen atmosphere is maintained.

-GC

 

[sekio]

You don't even need to use elemental hydrogen at all, transfer hydrogenation works using a myriad of hydrogen donors (ammonium formate works fine).

But this is being 'cooked' in peoples homes using easily acquired precursors

Is it really, though? I am not deeply connected to the Eastern Bloc opioid scene but the notion of home chemists making desomorphine as a massive problem doesn't hold water. It's like home shake-and-bake meth; yes people have done it, but overall the risk/reward doesn't hold up in light of the trivial cost of bulk produced cartel meth. Certainly it will have no commercial value on the street - I'd think anyone making such a mucky mess would be taking it themselves.

By that logic I would expect fentanyl and analogues to be a much more pressing problem, even if it's nowhere near as dramatic as people turning into drug addled zombies with flesh melting off their bones.

They cannot afford hydrogenation units let alone catalysts. It is a drug of the poor,

But they can somehow put the work in to source codeine tablets, extraction solvents/reagents, iodine, and red phosphorous?