Kratom Novel Mitragynine Drugs

[Twisted_Chemist]

7-methylmitragynine, A new novel Mitragynine molecule. I am sorry if I put this in the wrong place. I could not find the advanced drug discussion page.

This is just a proposed molecule, something I have been playing around with in my spare time at work.

If a methyl group (-CH3) were added to the 7th position of mitragynine, the resulting compound would be a novel analog of mitragynine. 7-methylmitragynine, would have a structure similar to mitragynine but with a methyl group attached to the third ring at the 7th position.

This could potentially increase the molecule's lipophilicity. This, in turn, could affect the compound's absorption, distribution, metabolism, and excretion in the body.

NOTE:
This modification would likely alter the molecule's physical and chemical properties, as well as its pharmacological activity.

So far I am still running the CADD simulations, but it looking very promising.
And before people complain, I am not looking at making this to get high, but as a fun research project to kill time at work and see what I can come up with. Odds are, it will amount to nothing.

Any thoughts or suggestions on how to add the methyl group, please let me know! The hardest part (or most expensive if you buy it) is getting the pure mit.

The other option, would be to fully synth the chemical. Not cheap and no easy feat.

Thoughts?

----
ToDO's

1) Protect the functional groups on the molecule that should not be modified during the alkylation process.

2) Treat the protected mitragynine with a suitable alkylating agent, such as methyl iodide or dimethyl sulfate, under appropriate conditions to introduce the methyl group at the 7th position.

3)Remove the protecting groups to reveal the modified molecule.

 

[Twisted_Chemist]

Reserved for second molecule I am researching.

 

[simstim]

I wonder what would happen to the activity if you methylated 7-OH-mitragynine to form 7-MeO-mitragynine.

There is 7-AcO-mitragynine. There is a thread about it. People seem to think it will hydrolize into 7-OH-mitragynine in the body.

It seems to me that 7-MeO, or as you mentioned 7-Me, might be better than 7-OH.

I believe methoxy and methyl are more alike than an OH. Like 3-ME-PCP seems a lot closer to 3-MEO-PCP than 3-OH-PCP.

Same for amphetamines. Para methyl seems more like para methoxy than para hydroxyl.

Let us know if you get it synthesized.

 

[simstim]

I am not sure how you would make 7-methyl-mitragynine. As in how to methylate it at that position.

Here is 7-methoxy-mitragynine.

 

[Jabberwocky]

Could alterations be made to mitragynine to give it tryptamine like effects?

 

[Skorpio]

Could alterations be made to mitragynine to give it tryptamine like effects?

I think you would need to remove so much bulk that you basically would just have 5-meo dmt.

Tryptamines don't handle having too much junk on the amine very well (I think butyl groups are where potency drop off occurs).

 

[simstim]

Could alterations be made to mitragynine to give it tryptamine like effects?

Well there is a residue of 5-methoxytryptoline that is more tryptamine in nature. The 6-methoxy analogue (pinoline) is an MAOI like other beta carbolines so I would not be surprised if 5-methoxytryptoline was as well. I just read a paper that said that 5-methoxytryptoline is an inhibitor of serotonin reuptake and that it disrupts binding of imipramine (https://pubmed.ncbi.nlm.nih.gov/2987413/).

So could be a combined reversible MAOI and is a serotonin reuptake inhibitor at the imipramine site.

I wonder if it would show any hallucinogenic effects like harmaline does in high doses? It is very close in structure.

It may not be safe in high doses being an MAOI and SRI.

5-methoxytryptoline

 

[simstim]

5-methoxytryptoline and close analogs as candidates for the endogenous ligand of the 3H-imipramine recognition site - PubMed

3H-Imipramine labels with high affinity a site associated with the macromolecular complex of the serotonin transporter in brain and platelets. There is a good correlation between the potencies of drugs at inhibiting 3H-5HT uptake and at inhibiting 3H-imipramine binding. Dissociation experiments...

pubmed.ncbi.nlm.nih.gov

 

[stom10]

Just spitballing here, as I'm not a synthetic chemist, but getting selective methylation of the 7 position from mitragynine as a starting material is not going to be an easy task at all.

 

[simstim]

Just spitballing here, as I'm not a synthetic chemist, but getting selective methylation of the 7 position from mitragynine as a starting material is not going to be an easy task at all.

I think so too. That's why I suggested 7-methoxy instead

 

[Didgital]

Gonna say this is likely impossible or uneconomical even if it is. The psuedoindoxyls/oxoindoles you could take a short cut using an interrupted ugi reaction. Might be something there.

And yeah I agree the 7 methoxy seems way more plausible.

Isolation of MIT has become a lot simpler btw, and it's probably a good starting point for related compounds.