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5HT2a ligands and RC Tryptamines

4-MeO-AMT is not a bad idea. It's logical and its not whacky. Still I have no personal ambition to process this information at present but if 5-MeO-AMT works, heh its got potential!
 
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Helios. said:
The new molecule (R-O-O-R) is called a dimer because it consists of two identical subunits connected to each other to form a bigger molecule. The R's in the new molecule, R-O-O-R, can be rightly called
4-(3-dimethylaminoethylindolyl's).

If this doesn't help explain it right, I'll scan a Kekule structure for you if possible.
Click to expand...

I wasn't confused about that.

I'm asking about the quinonic product Shulgin is talking about. Why are we talking about this dimer anyway ... we were talking about physiologically relevant reactions or changes in conformation, not degredation.
 
Well the whole rationale of 4-MeO-AMT is you can leave it sitting w/o having to worry about degradation.

Then upon ingestion, the Me-O- snaps off leaving OH.

Srsly I should be charging u for this. 4-Cl is a bullshit idea!
 
^^But the -meo doesn't snap off. It doesn't get hydrolysed easily like the ester or phosphoroloxy linkage.

Don't we need an atom that can hydrogen bond at that fourth position, like ... OXYGEN?

And btw Helios, I've never said this about anybody at BL, but you are a dick.

Fourthly, I wasn't saying that the quinone idea was true, but I was trying to figure out the relationship between that and the internal salt, which would have interaction between the 4-pos. oxygen and the tertiary amine.
 
Technically speaking, an oxygen already exists at the 4-position in the 4-MeO-AMT. I think you mean hydroxy since the acidic hydrogen at the 4-position is what is forming the H-bond in 4-OH-DMT. Im talking about decomposition. Its a pain in the ass for people who buy/make pure white crystals only to witness their goods turn to muck. I dont care if the muck can be prevented or is still active, it's still a bitch.

The Me-O bond will snap. It might not be an instant hit but after an hour or two things would be crawling.
 
Dondante said:
MadShroomer, do you even know what a quinone is?
Click to expand...
Actually, at first no except for what Shulgin was describing in the article SWIM quoted.
However SWIM did some more research but suddenly the Adderall medication quit working, then the ADD took hold and SWIM found that above college chem 101 things get a little fuzzy... 8(

Dondante said:
The quinone idea (I think) is very similar to C6H6's internal salt idea, although I have no idea how that product Shulgin is describing would be classified as a quinone. I think he's talking about a delocalized pi electron bond between the quinonic oxygen and the nitrogen that would occur after oxidation (maybe?) I don't really have much of a chem background so I'm not in familiar territory here.

I like the internal salt hypothesis, because it does not require oxidation like Shulgin's hypothesis. Also, I think there's a general consensus that a quinonic product would not be active ... so that would require reduction, which I don't see happening (just seems like too much work). The internal salt would possibly allow for a natural equilibrium between two conformations (one to get past the BBB and one to activate the receptor). Who knows? There are many possibilities. If someone could clear up what exactly this cross-conjugated product looks like I'd appreciate it.
Click to expand...

I like your idea. SWIM found [on another site...] a picture of the -H2 reaction with the 4-ho-dmt molecule that was being described in the article (I think..)
I'll find this now and post....
[2 minutes later]
We'll it appears it was on THIS site... in the Big and Dandy 4-AcO-dmt thread...
This probably isn't what you were talking about but I hope it helps...
attachment.php
 
Helios. said:
Smyth, the 4-MeO will not snap.

Dondante, when ionic bonds dissolve in aqueous media, they dissociate.
Click to expand...

Well, yeah except we're talking about a zwitterion with a strong intramolecular H-bond. Why don't you think it could keep that H-bond at least for the purposes of crossing the BBB. I'm sure some molecules will have H-bonds with H20, but that doesn't mean all of them do.

So you think that 4-HO-DMT isn't too polar and gets across the BBB no problem? That was my initial assumption, but I am starting to think that the polarity should be stopping it like with 4-PO-DMT.
 
Hey, Helios!
Why are you so sure that the "quinone-thing" is false?
Fact is, that this stuff becomes colored, and I doubt, that your peroxide-dimer is a colored compound.
But if you have evidence for the dimer, I find it very interesting!
Please give a short explanation!
-Thanx
 
A few thoughts about the quinonic product: in the stability study,I never saw one prominent side product however blue the solution turned.It looked rather like a degradation to a very broad range of products.I'm not saying the quinone wouldn't be active (hello Adrenochrome!),it just is not formed in meaningful amounts.If a reduction is necessary for activity,try hypoxic conditions.I'm currently working on quinonic molecules which are activated in vivo to the active hydrochinons, especially under hypoxic (tumor) cells.Certainly,synthesising the quinon would be conclusive :D

It really itches me that we don't know the stability of the acetyl there.Guess 0.5-1h at 30° in 0.1N HCl should be an appropriate experiment.
 
Dondante,

4-OH-DMT gets into the brain just fine, otherwise it wouldn't make your brain trip. 4-phosphate-DMT is dephosphorylized without delay upon ingestion. Morphine also gets into brain alright, and it too has hydroxy groups.

EN21,

I learned that second hand at the Hive, reputedly coming from a scientific journal. It makes sense to me.

hugo24,

adrenochrome indeed.
 
In scifinder there is no known "peroxide-styled" O-O dimer of tryptamines known.
Neither linked over the 4-oxygen of psilo-anything, nor linked over the 5 opsition (bufotenin/serotonin-stuff). Even not with "substructure search".

But searching for the concepts quinone and tryptamine gives many hits. They all refer to serotonin degradation products. There are many of dimers and oligimers, but no O-O-peroxides. They all are C-C linked and result from the reaction of the quinones.
Here are three references with abstracts:
Oxidation chemistry of 5-hydroxytryptamine. Part II. Mechanisms and products formed at millimolar concentrations in acidic aqueous solution. Wrona, Monika Z.; Dryhurst, Glenn. Dep. Chem. Biochem., Univ. Oklahoma, Norman, OK, USA. Journal of Electroanalytical Chemistry and Interfacial Electrochemistry (1990), 278(1-2), 249-67.

The electrochem. oxidn. of 5-hydroxytryptamine (5-HT) has been studied at a pyrolytic graphite electrode in aq. soln. at pH 2. The mechanism assocd. with the first voltammetric oxidn. peak Ia of 5-HT has been elucidated based upon electrochem. results and isolation and structural characterization of many products. An initial, reversible one electron abstraction generates a radical cation 5-HT.+ which, in a rate-controlling reaction, generates the neutral radical 5-HT. in which the unpaired electron is located at C(4). This radical is attacked by 5-HT to generate four simple dimers all of which contain at least one 5-HT residue linked at C(4). An unusual C(3)-C(4') linked indolenine-indole dimer can be oxidized further at peak Ia potentials to an indolenine-quinone imine dimer. The latter compd. is unstable and decomps. spontaneously to several products, three of which have been structurally characterized including an unusual quinoline-indole dimer. The C(4)-centered indolic radical 5-HT+ can be further oxidized to a quinone imine which is rapidly attacked by nucleophiles such as water or Cl- to yield ultimately tryptamine-4,5-dione and 4-chloro-5-hydroxy-tryptamine, resp.



Oxidation chemistry of 5-hydroxytryptamine. 1. Mechanism and products formed at micromolar concentrations. Wrona, Monika Z.; Dryhurst, Glenn. Dep. Chem., Univ. Oklahoma, Norman, OK, USA. Journal of Organic Chemistry (1987), 52(13), 2817-25.

The oxidn. of very low concns. (<30 mM) of 5-hydroxytryptamine (I) in 0.01 M HCl was studied by using electrochem. and other anal. techniques. The initial oxidn. is a 1e,1H+ reaction, giving a phenoxyl radical which exists in equil. with aryl, C(4).bul., and N(1).bul. radicals. At low potentials the latter radicals can react to give dimeric products. At higher potentials, however, the primary phenoxyl radical is further oxidized (1e,1H+) to a reactive quinone imine. The quinone imine is rapidly attacked by water to give 4,5-dihydroxytryptamine (II), which is further oxidized to tryptamine-4,5-dione (III). In aq. soln. at pH 2, III is slowly attacked by water to give 4,5,7-trihydroxytryptamine, which is further oxidized (2e,2H+) to 5-hydroxytryptamine-4,7-dione (IV). III and IV then react together to give a hydroxylated tryptamine dimer. The facile oxidn. of I to give at least two neurotoxins, II and IV, might provide insight into the previously proposed anomalous oxidative metab. of I as an underlying cause of various mental disorders.



Neurotoxic oxidative metabolite of serotonin: possible role in Alzheimer's disease. Volicer, Ladislav; Wrona, Monika Z.; Matson, Wayne; Dryhurst, Glenn. VA New England Health Care System, Boston University School of Medicine and Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, USA. Editor(s): Broderick, Patricia A.; Rahni, David N.; Kolodny, Edwin H. Bioimaging in Neurodegeneration (2005), 85-93. Publisher: Humana Press Inc., Totowa, N. J

A review. Excessive generation of reactive oxygen species and reactive nitrogen species in the Alzheimer's disease (AD) brain and the presence of serotonin in the brain regions that are damaged in this disorder may lead to oxidn. of serotonin to tryptamine-4,5-dione, which may possess neurotoxic properties. Efforts to detect this dione in brain tissue or cerebrospinal fluid of AD patients have been so far unsuccessful. However, it may be of relevance that the expression of NAD(P)H:quinone oxidoreductase 1 (NQO1), an enzyme that acts to protect against oxidative stress caused by xenobiotic quinones, is localized not only to neurofibrillary tangles in the AD brain but also to the cytoplasm of hippocampal neurons. In contrast, very little NQO1 is present in the same neuronal populations in age-matched controls. The expression of NQO1 in the AD brain not only provides addnl. support for excessive prodn. of oxygen free radicals but also, possibly, for a role of a quinone such as tryptamine-4,5-dione.

Additionally the fact, that the blue color disappears after the addition of antioxidants like vit.C is a hint that the quinones are colored and the resulting adducts without color.
 
fruitless.

If you have a new, original idea for a 5-HT2a ligand, then feel free to post it.

Otherwise, you're engaging in moot sophistry. Anyone can come up with theories as to why other people's discoveries work.
 
At first the peroxide idea seemed strange but now that I think about it isopropyl alcohol can form peroxides if left standing for a long enough time. I dont have Scifinder but it does only cover work done in the academic field and not all of the compounds being stewed up behind closed doors in the industrial pharm companies.
 
But I think its a hydroperoxide.

Oh,what did I miss re: adding Vitamin C to remove colour?
 
You mean the tear like goo which is formed?Quite likely,I had similar cases in the lab recently.And the bump in the baseline on the HPLC couldn't be more typical for that!
 
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