that's because it is zwiterrionic the phenol protonates the tertiary nitrogen.
Re: Naltrexone to oxymorphone idea
« Reply #20 on: February 04, 2012, 09:54:26 AM »
Topic: Naltrexone to oxymorphone idea (Read 274 times)
jon
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Assyl Fartrate
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Re: Naltrexone to oxymorphone idea
« Reply #21 on: February 04, 2012, 10:00:06 AM »
Just do an acid base and evaporate your material. It should be clean enough given a reaction like that. Dose with it diluted in water or alcohol of course.
jon
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Re: Naltrexone to oxymorphone idea
« Reply #22 on: February 04, 2012, 02:19:35 PM »
yeah with morphines and morphinones are zwitterionic and difficult to extract also when you overshoot your ph past 8.5-9 the phenol gets converted into a soluble salt so they are tricky to extract.
Assyl Fartrate
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Re: Naltrexone to oxymorphone idea
« Reply #23 on: February 04, 2012, 02:35:15 PM »
Whoops, you're right... reading comprehension failure over here, thought his product was a codone (thought he was making an ester for some reason). Guess it's better to demethylate oxycodone with plain HBr and not use any catalytic salts like LiBr, MgBr2, etc.
Do you know if any 3-acylated morphones can be extracted with a traditional acid base (assuming one works quickly enough to avoid extensive hydrolysis)?
Do you know if any 3-acylated morphones can be extracted with a traditional acid base (assuming one works quickly enough to avoid extensive hydrolysis)?
jon
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Re: Naltrexone to oxymorphone idea
« Reply #24 on: February 04, 2012, 02:41:14 PM »
no it's better to use a promoter because you can run the reaction at lower temperatures, minimizing damage to the phenanthrene skeleton.
yes 3-acyl morphones are'nt zwitterionic.
like i said the most important thing is ph when extracting morphine and friends.
that and copious solvent sometimes 2 dozen extractions are needed.
yes 3-acyl morphones are'nt zwitterionic.
like i said the most important thing is ph when extracting morphine and friends.
that and copious solvent sometimes 2 dozen extractions are needed.
Assyl Fartrate
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Re: Naltrexone to oxymorphone idea
« Reply #25 on: February 04, 2012, 02:44:54 PM »
Hmmm.... need to dig up some old notes, so the reference can be provided, but some group a while back tried to wreck oxycodone using all kinds of nasty dehydrating reagents, heat, etc... trying to get that 14-hydroxy to eliminate, but the molecule was seemingly invincible. The only thing that did anything was phosphorus pentoxide which destroyed it completely. It seems like an unusually resilient structure. Could be wrong though... it was just one paper.
jon
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Re: Naltrexone to oxymorphone idea
« Reply #26 on: February 04, 2012, 02:46:41 PM »
yeah i messed up some hydrocodone with HBr in acetic acid.
oxycodone has some peculiar properties.
oxycodone has some peculiar properties.
Assyl Fartrate
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Re: Naltrexone to oxymorphone idea
« Reply #27 on: February 04, 2012, 02:50:11 PM »
What happened with that? Heard completely contradictory reports on HBr demethylation of hydrocodone... anywhere from 90% yields to black tar, 0%...
jon
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Re: Naltrexone to oxymorphone idea
« Reply #28 on: February 04, 2012, 02:55:10 PM »
black tar is what i got.
both times once using 48% aq. HBr
and 25% HBr in acetic acid.
both times once using 48% aq. HBr
and 25% HBr in acetic acid.
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Re: Naltrexone to oxymorphone idea
« Reply #29 on: February 04, 2012, 07:54:27 PM »
Nice,a lot of good info here!
I had a big problem extracting morphine,especially from diluted water solution until I got an idea...
1.)Extract your morphine from whatever using diluted AcOH water solution.
2.)Salt the hell out of your morphine containing water solution,NaAcO seems to be ideal.
3.)Cool it. Add Na2CO3 solution,drop by drop until you get 8.5-9.5 pH (9.1 is ideal)
4.)Morphine freebase should participate in form of small needle like crystals quantitatively.
5.)Filtrate,dry well and esterify. there should be enough NaAcO in dry product for catalysing esterification.
If you want to extract pure morphine from from mixture of various opiates (codeine,thebaine etc...)
after step 2.) basify carelessly (12-14pH) with strong base and extract participate with non polar like Et2O. Those are other opiates.
Now add some acid in basic water solution,drop by drop,until you are at 8.5-9.5 pH and collet morphine like i mentioned.
I had a big problem extracting morphine,especially from diluted water solution until I got an idea...
1.)Extract your morphine from whatever using diluted AcOH water solution.
2.)Salt the hell out of your morphine containing water solution,NaAcO seems to be ideal.
3.)Cool it. Add Na2CO3 solution,drop by drop until you get 8.5-9.5 pH (9.1 is ideal)
4.)Morphine freebase should participate in form of small needle like crystals quantitatively.
5.)Filtrate,dry well and esterify. there should be enough NaAcO in dry product for catalysing esterification.
If you want to extract pure morphine from from mixture of various opiates (codeine,thebaine etc...)
after step 2.) basify carelessly (12-14pH) with strong base and extract participate with non polar like Et2O. Those are other opiates.
Now add some acid in basic water solution,drop by drop,until you are at 8.5-9.5 pH and collet morphine like i mentioned.
Oerlikon
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Re: Naltrexone to oxymorphone idea
« Reply #30 on: March 30, 2012, 12:58:57 AM »
I was curious...
Since most of the (available) opiate antagonist are nothing but extremely potent
agonists with one "special" group attached to the N.
It's mostly cyclopropyl or alkene group. Both behave allmost same,creating covalent bound to the
desired place in receptor and effectively neutralizing it.
So,does any one of you know any (simple/home-friendly) method that will easily remove,change or
saturate that party-breaking group, thus making former antagonist come to the dark side!
If you menage,for example,saturate 17-cyclopropylmethyl group on naltrexone and get 17-butyl group instead,
will that extra length in chain on position 17 make resulting agonist stronger or weaker?
Catalytic hydrogenation might be an answer,but how to prevent it from fuck-up ketone on the 6th position
and other parts of molecule?
Since most of the (available) opiate antagonist are nothing but extremely potent
agonists with one "special" group attached to the N.
It's mostly cyclopropyl or alkene group. Both behave allmost same,creating covalent bound to the
desired place in receptor and effectively neutralizing it.
So,does any one of you know any (simple/home-friendly) method that will easily remove,change or
saturate that party-breaking group, thus making former antagonist come to the dark side!
If you menage,for example,saturate 17-cyclopropylmethyl group on naltrexone and get 17-butyl group instead,
will that extra length in chain on position 17 make resulting agonist stronger or weaker?
Catalytic hydrogenation might be an answer,but how to prevent it from fuck-up ketone on the 6th position
and other parts of molecule?
jon
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Re: Naltrexone to oxymorphone idea
« Reply #31 on: March 30, 2012, 03:27:01 AM »
the theory is that the phenyl propyl group changes the opiod receptor confirmation.
our theory is the hydrocinnnamyl ester can be made in 2 steps and act in a similar manner to the ether because the cinnamyl ester is a mixed agonist and the phenyl propyl ether is an agonist, due to the greater confirmational freedom of the ring.
in fact one of the authors of the schmidhammmer paper seemed to have the same opinion. pretty good bet it would work.
the paper below should clarify things greatly for you.
our theory is the hydrocinnnamyl ester can be made in 2 steps and act in a similar manner to the ether because the cinnamyl ester is a mixed agonist and the phenyl propyl ether is an agonist, due to the greater confirmational freedom of the ring.
in fact one of the authors of the schmidhammmer paper seemed to have the same opinion. pretty good bet it would work.
the paper below should clarify things greatly for you.
63349878-The-Opiate-Receptor-A-Model-Explaining-Structure-Activity-Relationships-of-Opiate-Agonists-and-Antagonists-PNAS-USA-1976-73-11-4215.pdffresh1
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Re: Naltrexone to oxymorphone idea
« Reply #32 on: March 30, 2012, 07:09:24 AM »
hey matey have did you know they recently decoded opiate receptors recently? (thats a pretty old paper btw with a LOT of speculation, not dissin, just sayin 
)
http://www.nature.com/news/opioid-receptors-revealed-1.10273
care to elaborate amigo?
)Quote
21 March 2012
Article tools
On a small table in his office at the Scripps Research Institute in La Jolla, California, Ray Stevens spreads out a sheet of paper covered with colourful branched lines, each sprouting and thinning before terminating in an esoteric code. “This is the dream,” he declares.
The intricate diagram represents the largest family of receptor proteins encoded in the genome — the G-protein-coupled receptors (GPCRs), ubiquitous cell-surface molecules that are activated by light, odours, hormones and neurotransmitters. Stevens wants to determine the atomic structures of receptors on all branches of the tree. This week, that goal moved two receptors closer: Stevens's group has solved the atomic structure of the ?-opioid receptor (?-OR)1, and a team led by Brian Kobilka at Stanford University in California has solved the medically crucial ?-opioid receptor (?-OR)2. The structures, published in Nature, bring the tally of GPCR structures solved this year alone up to five
http://www.nature.com/news/opioid-receptors-revealed-1.10273
Quote
our theory is the hydrocinnnamyl ester can be made in 2 steps and act in a similar manner to the ether because the cinnamyl ester is a mixed agonist
care to elaborate amigo?
jon
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Re: Naltrexone to oxymorphone idea
« Reply #33 on: March 30, 2012, 07:20:37 AM »
i thought i did.
the 14- beta -o- phenyl propyl ether of naltrexone is 400-600 times the potency of morphine.
the synthesis requires 4 steps: 6- keto protecction, 3-phenol protection, 14-o alkylation and deprotection of the 3 and 6 postions.
well i hypothesize that the hydrocinnamyl ester (14-o phenyl propyl ester) is also an agonist as is the phenyl propyl ether.
since, it has the same geometry practically speaking as the ether and it can be synthesized by bis acylation 3 and 14 acylation followed by selective hydrolysis of the phenolic ester with dilute sulfurinc acid or potassium carbonate.
the cinnamyl ester with it's double bond restricts the freedom of the benzene ring and it is a mixexd agonist if you study that paper i just linked it will all become clear.
you will see that the potent agonists like fentanyl for example have that phenylethyl tail like this does with it's phenylpropyl ether and the ring is axial in relation to ring a.
much more practical and likely to work.
the 14- beta -o- phenyl propyl ether of naltrexone is 400-600 times the potency of morphine.
the synthesis requires 4 steps: 6- keto protecction, 3-phenol protection, 14-o alkylation and deprotection of the 3 and 6 postions.
well i hypothesize that the hydrocinnamyl ester (14-o phenyl propyl ester) is also an agonist as is the phenyl propyl ether.
since, it has the same geometry practically speaking as the ether and it can be synthesized by bis acylation 3 and 14 acylation followed by selective hydrolysis of the phenolic ester with dilute sulfurinc acid or potassium carbonate.
the cinnamyl ester with it's double bond restricts the freedom of the benzene ring and it is a mixexd agonist if you study that paper i just linked it will all become clear.
you will see that the potent agonists like fentanyl for example have that phenylethyl tail like this does with it's phenylpropyl ether and the ring is axial in relation to ring a.
much more practical and likely to work.
fresh1
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Re: Naltrexone to oxymorphone idea
« Reply #34 on: March 30, 2012, 08:19:49 AM »
Quote
i thought i did.
lol
sorry matey I should bee more clear in my questions, ok I basically see the process of the reaction, I only speed read the paper (sorry, its very interesting and I'd like to give it the time it deserves) so I was curious as to this comment
Quote
the hydrocinnnamyl ester can be made in 2 steps
How would you go about doing this i.e. feedstocks and reagents, rxn conditions etc fresh still has a looong way to go to know enough to work this out
jon
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Re: Naltrexone to oxymorphone idea
« Reply #35 on: March 30, 2012, 09:07:52 AM »
read the supplemental on that paper on the cinnamoyl ester i posted above.
fresh1
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Re: Naltrexone to oxymorphone idea
« Reply #36 on: March 30, 2012, 09:14:58 AM »
I think I'm missing something here...I'll have a better look!
I find it amazing how just a few carbon atoms can change a molecule from an agonist into an antagonist! e.g. M and naloxone
ps. thats a great paper . . . I wish I had seen it a few years ago
I find it amazing how just a few carbon atoms can change a molecule from an agonist into an antagonist! e.g. M and naloxone
ps. thats a great paper . . . I wish I had seen it a few years ago
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Re: Naltrexone to oxymorphone idea
« Reply #37 on: March 30, 2012, 10:59:19 PM »
It may also be possible to take a shortcut to the ether: acylation, and if selective for the aliphatic OH proceed immediately with reduction to the ether, otherwise gentle hydrolysis of the phenolic ester first. Aliphatic esters can be reduced to ethers with indium salts and triethylsilane.
hxxp://pubs.acs.org/doi/abs/10.1021/jo070814z
hxxp://pubs.acs.org/doi/abs/10.1021/jo070814z
jon
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Re: Naltrexone to oxymorphone idea
« Reply #38 on: April 01, 2012, 02:17:35 AM »
i thought of that too with lah but it would reduce both 6 keto and 3-oh would neuutralize lah or borane.
you still gotta o protect.
that's why i'm speculating that ester would be similar to the ether, it meets all the requirements.
if not i'm going to shelf it for a simple click reaction with pyridyl-3-sulfonyl azide and methylpiperidine to knaus opi8.
it does'nt get easier than that.
remember that paper on agonists/antagonists places emphasis on the position and orientation of ring f and the hydrocinnamyl ester satisfy these requirements.
you still gotta o protect.
that's why i'm speculating that ester would be similar to the ether, it meets all the requirements.
if not i'm going to shelf it for a simple click reaction with pyridyl-3-sulfonyl azide and methylpiperidine to knaus opi8.
it does'nt get easier than that.
remember that paper on agonists/antagonists places emphasis on the position and orientation of ring f and the hydrocinnamyl ester satisfy these requirements.