(N-Acetyl) - L-Tyrosine as a replacement for Pseudo-Ephedrine

Gaffy

Bluelighter
Joined
Oct 27, 2018
Messages
147
Location
LE PEcq
FIRST OF ALL: Never snort pure N-Acetyl-Tyrosine; it's the most painful thing I've experienced so far( It does have a kick though).
I'm currently on 5mg Haldol Decanoate/ day and am taking 400mg caffeine and 60mg PseudoEphedrine twice a day to combat depressive feelings of tiredness and laxism that come with it. Will Tyrosine affect my mood and overall stimulation, and how does 500mg of it compare to 60mg Pseudo. I will probably take it in combination with the pseudo in the Morning and skip pseudo at midday.

Also I'll try to make 4-Methoxy Methoxyphenylalannine with it (supposed adrenergic/cholinergic); I'll report back on it.

Do post any experiences or research you've got on the sub.

Older posts of interest:
 
Last edited:

sekio

Moderator: N&PD
Staff member
Joined
Sep 14, 2009
Messages
19,465
Location
streets of simcity
pseudoephedrine is a better decongestant than stimulant, it has barely any central activity as a stimulant and produces mostly peripheral effects (increased b.p., relief of nasal congestion etc).

tyrosine and its friends don't have central stimulant effects either, normally your body gets all the tyrosine it needs from hydrolysis of dietary proteins, it's Just Another Amino Acid basically. as I keep pointing out, the rate limiting step of dopamine synthesis is the enzymatic conversion of tyrosine to L-DOPA (i.e. the enzymes in your body can only convert a fixed amount of tyrosine to LDOPA per unit of time and taking more tyrosine does not speed this process up), so unless you are deficient in phenylalanine/tyrosine then ingesting more won't do much at all.

also unless you have lab experience I somehow don't see you making 4-meo-phenylalanine, it takes more than boiling tyr in methanol to make it... (protecting both the -COOH and -NH2 groups, then alkylating the 4'-phenol with e.g. MeI and K2CO3, then deprotecting -COOH/NH2)
 

Hodor

Bluelighter
Joined
Jul 3, 2009
Messages
1,630
Also I'll try to make 4-Methoxy Methoxyphenylalannine with it (supposed adrenergic/cholinergic); I'll report back on it.
You can't just turn a phenol into an ether like that.

Even acetylating a phenol into an ester (à la morphine => heroin) requires the use of a strong acetylating agent (typically acetic anhydride) and continuous refluxing.

What you're trying to make, however, is an ether. This is an even more challenging process, requiring strong alkylating agents (like methyl iodide or dimethyl sulphate) and a sufficiently strong base to deprotonate the phenol. Needless to say, such alkylating agents are not something one should handle without a well-equipped lab (especially a fume hood!), as these are carcinogenic.

Heating tyrosine in methanol would at best methylate the carboxyl group, but you're not going to make a phenol ether that way, sorry.
 

Gaffy

Bluelighter
Joined
Oct 27, 2018
Messages
147
Location
LE PEcq
I want the COOH to methylate as well, like the chem in the ILTD thread. And as it is N-acetyl tyrosine I guess the amine is protected enough.
I saw a post on reddit where someone turend IPPH into MPH by leaving it in pure MetOH for a few days; I Believe Roi pointed this out some while ago. It's a slow reaction but it works.


What it'll probably look like:

 
Last edited:

Skorpio

Bluelighter
Joined
May 11, 2011
Messages
149
Methanol isn't a methylation agent.

You probably shouldn't be doing home synthesis if you need to be told this, especially using formic acid and formaldehyde on something you plan to consume.
 

sekio

Moderator: N&PD
Staff member
Joined
Sep 14, 2009
Messages
19,465
Location
streets of simcity
hydrolysis is the reaction of esters with water to form an alcohol and carboxylic acid, e.g. methylphenidate undergoes hydrolysis in the body to form its primary metaboilite, ritalinic acid; or triglycerides undergoing hydrolysis to glycerin plus free fatty acids.

the reaction between esters and alcohols is more correctly called a transesterification reaction



both of these involve attack on the carbonyl of the ester group by the incoming alcohol or water, forming a tetrahedral center that then rearranges with the expulsion of an alkoxy group to form a new ester (or acid in the case of hydrolysis, e.g. where R2 = H)

normally these reactions need catalytic acid or base to run, they do not occur readily in neutral media

when attempting synthesis of esters from alcohol + carboxylic acid, known as a Fischer esterification, the reaction governing formation of the ester will compete with the hydrolysis of the same ester (remember for every 1 mole of formed ester, you're forming 1 mol of water, which can then react with the ester to bring you right back where you started). hence you get a situation known as a chemical equilibrium where, depending on the concentrations of the initial reactants you will not have 100% conversion, yields are generally low unless you have some other method to remove the formed water or ester (distillation, etc). so most chemists would rather e.g. form an acid chloride using an activating agent like SOCl2 so there is no water at all to worry about and the reaction goes to 100% completion easily. oh also fisher esterification can be really slow (reaction times in the hours to days) so yeah

oh also you can hydrolyse amides the same way (much slower but still possible to do, cat.acid+water+amide=amine+carboxylic acid)

tl;dr boiling carboxylic acids in methanol is not a good way to make an ester

and even if you did how would you propose to verify you have an ester? determining the titratable acidity with indicator? TLC? IR spectrum? or do you have a NMR, HPLC, GC machine handy?
 

Gaffy

Bluelighter
Joined
Oct 27, 2018
Messages
147
Location
LE PEcq
I have citric acid, 90° denatured alcohol and wwwaaay too much tyrosine. Based on the reaction procedure you posted, I guess adding citric acid isn't an option (is this right?)


As to how I'll propose I got an ester: I'm only interested in effects; hence I'll be taking normal tyrosine (which I can definitely feel working right now - I recommend adding citric acid to the water to help absorption) and whatever I get out of the reaction with alcohol, and judge based on how I feel if it's Worth keeping. (Can't be too toxic based on what I put in the pan..)
I'll heat it in a closed glass beaker au bain-marie, hope that works.

EDIT:

So I Added around 5grams citric acid as it's only a catalyst, around 100g N-acetyl-tyrosine and 125ml 90° Ethanol (with 2% isopropanol and butanol) and am heating it at around 95 °C in a bain-marie. The solution turend yellow upon addition of citric acid, heads up if you know why..
I'll leave it there as long as Sekio suggested, more than 24 hours. The problem I didn't think of is the extraction afterwards. I was thinking about drying it in a pan but I'm worried about the flamability of the fumes, so I'll probably add 50-100g of caffeine (the dose of caffeine I take /day is the same as the dose of tyrosine), freeze the solution and go with what I get out of it. +The caffeine will neutralise any acidic residue (unreacted citric acid) as it is caffeine base.

The crystals shown below are very gluey and the humidity won't properly evaporate; It's the citric acid (its pure form feels like glue). I'll neutralise it with caffeine, too bad it won't be crystals anymore (or might it just be? )
Sekio, you who do have everything at hand to prove you've gotten an ester, why not try it aswell to verify that what I've done is correct? You can claim the discovery of a new adrenergic and cholinergic RC.

Some pictures:

after 5minutes:




After 20 minutes:

You can see the solution boiling (I'm hoping the glass won't break because of the bar inside); also the glass isn't in direct contact with the heat so it shouldn't break because of that. (happened once before)






Two hours (very slight change in colour):




Looks nice, tastes horrid, isn't finished.




Turning cloudy:
 
Last edited:

Gaffy

Bluelighter
Joined
Oct 27, 2018
Messages
147
Location
LE PEcq
Ingested. Feeling very clearheaded, did some working out and can't feel any fatigue.
I've still got half my tyrosine and can get more Ethanol, reproceed without citric acid?
And I'm thinking that this would feel even better with some SER action; I'll try and get my hands on 5-HTP and do the same.
 

sekio

Moderator: N&PD
Staff member
Joined
Sep 14, 2009
Messages
19,465
Location
streets of simcity
you do realize that amino acid esters are broken down in the gut quite rapidly? And if you mixed a crapload of caffeine in there and cooled it down what you have is probably mostly caffeine by weight? and that tyrosine has no effect beyond placebo?

discovery of a new adrenergic and cholinergic RC.
this compound does neither, and is not "new", sigma sells it

also is it just me or are you heating alcohol in a jam jar with the lid screwed on??? do you want to be injured by an exploding glass jar full of alcohol? you should never heat a sealed apparatus unless it's specifically designed for pressure operations. glass jars are not pressure-tested nor heat-stress-tested.

please stop and spend some time getting a proper education, go watch some nilered videos or something instead of doing cowboy hackney shit that will get you injured or killed.
 

Gaffy

Bluelighter
Joined
Oct 27, 2018
Messages
147
Location
LE PEcq
You're right I made a mess. People if you try this don't add citric acid unless you want gluey untasty crystals (not to bad). Also, like me, make sure to slightly unscrew the top just enough for pressure to pass trough.

Btw sekio your name is now famous in my area under the name 5ELO, msg me if you want to hear te funny story behind it. (Really is something)
 

Hodor

Bluelighter
Joined
Jul 3, 2009
Messages
1,630
I have citric acid, 90° denatured alcohol and wwwaaay too much tyrosine. Based on the reaction procedure you posted, I guess adding citric acid isn't an option (is this right?)
This picture shows a carboxylic acid anhydride, not an ester. This compound would immediately hydrolyze upon contact with the water on your tongue, turning back into its constituent acids (which is also why you couldn't synthesize it in an aqeous solution).
 

Hodor

Bluelighter
Joined
Jul 3, 2009
Messages
1,630
OP, you seem to be missing sekio's point here: You can "methylate" a carboxylic acid into an ester using methanol because the carboxylic acid has a relative lack of electrons on the carbon atom, which the methanol can satisfy by offering the electrons on its oxygen atom.

This means that esters can form under "relatively" mild conditions.

However, by trying to condense methanol with tyrosine (which is a phenol, i.e. also type of alcohol), you aren't making an ester, you're creating an ether. The only way to create an incentive for the two alcohols to react like that would be to perform the reaction in concentrated sulfuric acid (which would bind any H2O released by the condensation reaction, thus shifting the chemical equilibrium); however, this is not an option here either because the H2SO4 would completely destroy the tyrosine.

Instead, you would have to first treat the tyrosine with a strong base to deprotonate the phenol, then react it with an actual methylating agent (i.e. something like dimethyl sulphate oder methyl iodide).
Needless to say, these toxic reagents should not be used in your freaking kitchen, using jam jars as glassware.
 

Gaffy

Bluelighter
Joined
Oct 27, 2018
Messages
147
Location
LE PEcq
All in all I can say that Tyrosine does have an effect on my mood and overall wellness, especially in association with pseudo-ephedrine and caffeine, and I strongly recommend taking 300mg once a day at midday.
 

Bravoncius Roxford

Bluelighter
Joined
Feb 1, 2017
Messages
54
FIRST OF ALL: Never snort pure N-Acetyl-Tyrosine; it's the most painful thing I've experienced so far( It does have a kick though).
I'm currently on 5mg Haldol Decanoate/ day and am taking 400mg caffeine and 60mg PseudoEphedrine twice a day to combat depressive feelings of tiredness and laxism that come with it. Will Tyrosine affect my mood and overall stimulation, and how does 500mg of it compare to 60mg Pseudo. I will probably take it in combination with the pseudo in the Morning and skip pseudo at midday.

Also I'll try to make 4-Methoxy Methoxyphenylalannine with it (supposed adrenergic/cholinergic); I'll report back on it.

Do post any experiences or research you've got on the sub.

Older posts of interest:
Tyrosine has no effect on central catecholamine synthesis because the body has a series of checks&balances to keep their levels at a homoestatic balance. This includes the amount of tyrosine that crosses the blood-brain barrier, the amount that gets converted into l-dopa by tyrosine hydroxylase, the amount that gets broken down before any conversion and expelled, and then the amount of norepinephrine and dopamine that gets oxidized by MAO and removed from the synaptic cleft by the norepinephrine and dopamine transporters(respectively). You cannot "cheat" your way to higher levels of norepinephrine and dopamine by taking tyrosine because the body has a series of redundant mechanisms to keep it's level in check. Also, extremely high levels of catecholamines produce problems like hypertension and cognitive deficits, so this is not necessarily a bad thing. The only scenario where taking tyrosine would result in a sharp increase in central norepinephrine/dopamine would be in the case of severe protein deficiency. Yes, taking tyrosine can increase your NE and dopamine massively...if you suffer from Kwarshiorkor and have ingested only white rice for the past 3 months. However, this does not apply to 99.9999% of all the people living in the West. In fact, the problem of Western diets, among other things, is an excess of protein and not a deficiency of it. The average American ingest almost 200 grams of protein a day, and tyrosine is abundant in animal proteins like meat and eggs. Even then, the body can convert phenylalanine into tyrosine if needed since tyrosine is not an essential amino acid. It is extremely unlikely that you ingest far less phenylalanine and tyrosine than needed daily and would benefit from supplemental tyrosine.

Increasing your NE and dopamine is possible by taking l-dopa with an l-aminoacid-decarboxylase inhibitor like carbidopa. L-dopa is the direct precursos to dopamine and crosses the blood-brain barrier much better than tyrosine, and carbidopa stops the l-dopa from being converted into dopamine in the body allowing more of it to get into the brain. You can also increase NE/dopamine levels by taking l-dopa even without carbidopa in the case of an extremely massive dose, say 100 grams of l-dopa taken at once. They use this protocolto increase dopamine for people with Parkinson's Disease. However, it is important to point out that this is a very bad idea unless you have late-stage Parkinson's. Higher levels of dopamine produce serious movement disorders and increased oxidative stress in the brain. It can also cause psychosis if the levels increase too much. You might try this if you are a very heavy stimulant abuser and want to ease withdrawal, but you should only do this under the supervision of an expert doctor. L-dopa therapy is so toxic and has so mnay side effects that they only do it in the case of late-stage Parkinson's. For early stage Parkinson's, they use MAO inhibitors like selegiline and rasagiline as monotherapy. That is because l-dopa + cabidopa is no joke when it comes to side effects.
 
Top