I Like to Draw Pictures of Random Molecules

[JacksinPA]

A very interesting 2-AT is MDAT, the methylene ether derivative of 6,7-ADTN. From the Wikipedia aricle:

6,7-Methylenedioxy-2-aminotetralin (MDAT) is a drug developed in the 1990s by a team at Purdue University led by David E. Nichols.^[1] It appears to act as a serotonin releasing agent based on rodent drug discrimination assays comparing it to MDMA, in which it fully substitutes for, and additionally lacks any kind of serotonergic neurotoxicity.^[1] Hence, MDAT is considered likely to be a non-neurotoxic, putative entactogen in humans.

https://en.wikipedia.org/wiki/Empathogen–entactogen

I found nothing on the stereochemistry of the amine group. & I don't have access to the J Med Chem article where it was made & tested. Has this ever been encountered as a RC?

 

[sekio]

Has this ever been encountered as a RC?

If memory serves, this was advertised for sale at around the same time people were hawking MDAI, 5-IAI, and the other indane/tetralins. But it's worth taking that with a grain of salt; especially if the synthesis is more complex than a 2- or 3-step "bucket" recipe - complicated synthesis plus pre-existing stocks of similar drugs that aren't selling well adds up to a grand total of... every unscrupulous vendor under the sun selling lots of shit drugs like 4-methoxymethcathinone as whatever the pill-popping public requests, be it "mephedrone", "benzo fury", "bath salts", "E", "pills"...

I don't have access to the J Med Chem article where it was made & tested.

In this day and age, EVERYONE has access to such things, just find the DOI (Digital Object Identifier) and plug it into Sci-Hub or Library Genesis (Libgen), like so: https://sci-hub.tw/10.1021/jm00164a037 ... and you get a PDF for downloading or reading, free of charge.

 

[JacksinPA]

In this day and age, EVERYONE has access to such things, just find the DOI (Digital Object Identifier) and plug it into Sci-Hub or Library Genesis (Libgen), like so: https://sci-hub.tw/10.1021/jm00164a037 ... and you get a PDF for downloading or reading, free of charge.

I live by the axiom that a day passing without learning something new is a day wasted. These tools were new to me, so thanks for the info. Libgen wouldn't work for me but Sci-Hub produced a pdf of the Nichols paper. See https://sci-hub.tw/10.1021/jm00164a037. This result amazed me knowing the strict copyright requirements of the ACS. In scanning this paper it appears that the MDAT used in the rat discrimination studies was racemic, which would eliminate the steps involved in resolving it in order to get a chiral active drug molecule. I'm curious to see if studies were done to study the relative activities of the R & S forms of MDAT give the strict chiral requirements in the related 6,7-ADTN. A Google search for 'chiral or R or S MDAT' produced no results.

Reading the experimental details in this paper is a reminder that Nichols (since retired I think) was working with a team of M.S. & Ph.D.-level graduate students & that the equipment, methods & chemicals used would be exactly like the ones they would be using when they went to work as research chemists for Merck or Pfizer. Paar shakers for catalytic hydrogenation, NMRs & Kugelrohr apparatus for high-vacuum short path distillation would usually not be found in the typical home lab. And anyone contemplating volume production would need a well-equipped pilot plant with lots of accessories.

 

[Pomzazed]

NMR in home lab? Wow!

 

[JacksinPA]

And a lot more beside. The primary purpose of the NMR is to verify the identity of each product as it is isolated. IR is still also widely used for this purpose.

 

[JacksinPA]

And a lot more beside. The primary purpose of the NMR is to verify the identity of each product as it is isolated. IR is still also widely used for this purpose.

I'm sure there are contract labs who will provide an NMR from a small sample but I'd think they would not be cheap. And besides that the operator might be studied enough to use the spectrum of your sample to deduce the structure. So unless you were in with them somehow or representing a big company, the ID of your sample might come to the attention of either the DEA or a blackmailer who would want some of your stash. Crap like that can & does happen.

 

[S.J.B.]

NMR in home lab? Wow!

You can get benchtop NMR instruments nowadays, but they definitely aren't cheap.

I'm sure there are contract labs who will provide an NMR from a small sample but I'd think they would not be cheap. And besides that the operator might be studied enough to use the spectrum of your sample to deduce the structure. So unless you were in with them somehow or representing a big company, the ID of your sample might come to the attention of either the DEA or a blackmailer who would want some of your stash. Crap like that can & does happen.

Universities around here with NMR facilities allow NMR time to be purchased by external researchers: the prices are reasonable, and I think you would be able to run the sample yourself. That said, if you aren't affiliated to a known company, the facility manager might be wary and check out what you were analyzing...

 

[Pomzazed]

Benchtop NMR is not that useful for this kind of research. At 60 MHz and requiring high concentration.
Also it doesnt decouple C, then that is seen is alot of island peak and broad overlapping main peak.

Mostly useful with small uncomplicate things with mw like < 350, without many groups.
Useful for routine checkup type of work.

Trust me, i tried these many brands,...
Thats why i said wow nmr in home lab...

 

[DotChem]

2-methyl-THBC aka "Russian Olive"

1, 2, 3, 4-Tetrahydro-2-methyl-b-carboline is found in fruits of Elaeagnus angustifolia. Elaeagnus angustifolia, commonly called Russian olive,^[1] silver berry,^[2] oleaster,^[2] Persian olive,^[2] or wild olive,^[2] or commonly referred to as senjhor or sinjhor in Pakistan, sinjid in Afghanistan , Iydə in Azerbaijan, senjed in Iran and p'shat (փշատ) in Armenia, is a species of Elaeagnus, native to western and central Asia, Afghanistan, from southern Russia and Kazakhstan to Turkey, Iran and parts of Pakistan. It is now also widely established in North America as an introduced species. ..

In Iran, the dried powder of the fruit is used mixed with milk for rheumatoid arthritis and joint pains. It is also one of the seven items which are used in Haft Seen or the seven 'S's which is a traditional table setting of Nowruz, the traditional Persian spring celebration.. wiki

looks like a restricted DMT

where one of the methyl of DMT is connected to the indole ring.. wonder it has any DMT-like activity (different from harmane and harmaline betacarbolines)

 

[JacksinPA]

This stuff is available in bulk (5-10 kgs) plus LTL ocean freight from sources such as Alibaba in China. Unless you are skilled in this sort of transaction, I'd be leery. (Been watching Season 2 of The Wire which is set on the Baltimore docks).

The fruit material contains a complex mixture of flavonoids, sterolds, anthocyananins, alkaloids, etc. See
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108988/ Extracting the alkaloid (basic) fraction might be as simple as putting it into a blender with hydrochloric acid, filtering off the solids, then letting the acid evaporate. You're still going to wind up with a mixture of compounds with uncertain biological properties. I couldn't find anything on psychoactivity. Seems like a lot of effort & expense to obtain a questionable final result.

BTW, what do you use to draw your structures?

 

[DotChem]

Extraction is probably not the best way to go for this specific compound. Easily accessible from tryptamine via straighforward easy Pictet Spengler rx or by methylation of pinoline eg in formic acid (will give the 5-methoxylated congener tho). It is way much cheaper to synthesize and you avoid bunch of other alkaloids, flavonoids..etc than extraction from fruits. the question really is if it might have same psyhoactivity as DMT: it is just its ring restricted isomer, isn't it? and very close to Pinoline:

Pinoline (presumably syntheszed in the pineal gland of humans! just like DMT presumably!!) is rather interesting molecule: it has potent neurogenesis activity, like 5HT2a agonist psyhedelics LSD, NBOM.etc. even at trace concentration!

Mario de la Fuente et al. 2015 "Neurogenic Potential Assessment and Pharmacological Characterization of 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin–Pinoline Hybrids" http://pubs.acs.org/doi/abs/10.1021/acschemneuro.5b00041

which makes me think it might have DMT-like psychoactivity. I couldnt find anyhthing on that specific compound either..


As for chem drawing, I use ChemAxon MarvinSketch. It is way better than ChemDraw or ChemSketch. Has way more features. You can actually use it in ChemDraw mode or ChemSketch if you like besides other options. The free version has tons of features besides simple 2D drawing such as conformation analysis, superimpose and compare 2 or more molecules conformations in 3D, predict parameters like pKa, cLogP, water solubility.etc. Or scan database (pubchem, surechem.etc) for 3D similarity to your structure..The paying version is even more powerful allowing molecule docking in proteins..etc but even the free version is pretty powerful if you don't mind annoying "subscribe to the full version " popup every time you fire the software.. check'em out: https://chemaxon.com/products/marvin

 

[JacksinPA]

Thanks for the (hopefully) helpful info on chem drawing. I love ChemDraw but life goes on.

I see a number of problems with your suggested approach: where & how are you going to get yourself 100-500 gr of tryptamine? When I worked for a big chemical company getting samples from other companies was not a problem. Tryptamine does not appear on the DEA Orange List (dea watch list). It is available from multiple Chinese sources, one of whom even accepts PayPal! (http://www.globalsources.com/si/AS/Shanghai-City/6008846763756/pdtl/Tryptamine/1057243520.htm). It might be easier to go from that straight to DMT though I don't want to get involved with synthesis methods here.

Caution: I'd request a small sample first & check the M.P. Some years ago a lot of people got ill from contaminated tryptophan that came from the Orient. These GNC-type health food stores may not be high on the QC scale.

Another idea based on tryptophan is to find a way (enzymatic or thermal?) to decarboxylate it to tryptamine. Here's a start: https://erowid.org/archive/rhodium/chemistry/tryptophan.html

 

[DotChem]

..It might be easier to go from that straight to DMT though I don't want to get involved with synthesis methods here...

yeah no synthesis discussion of specific compound is allowed on BL but for general info and sake of the safety of kitchen-chemists who might consider attempting to get dmt from tryptamine: commonly used methods of amines methylation by reductive methylation say in formic acid doesnt work in the case of tryptamine: the intermediate almost always cyclizes to give a betacarboline (you can't avoid that ..). it's almost always the major product & hard to separate from an intractable mixture of n-methyltrypatamine, nn-dimethyltryptamine, n-methylcarbolines, starting tryptamine..etc So lest you used direct methylation with nasty toxic cancer-causing chemicals like MeI, dimethylsulfate..etc... anyhow not wanting to discuss any chemistry but just so anybody trying to attempt that in his/her kitchen at home and reading this be warned.

..Another idea based on tryptophan is to find a way (enzymatic or thermal?) to decarboxylate it to tryptamine. Here's a start: https://erowid.org/archive/rhodium/c...ryptophan.html.

There are easier and milder methods that use microwave oven to decarboxylate alfa aminoacids.. shorter times (minutes not days!) and higher yields

 

[JacksinPA]

I've been giving the N-methylation of tryptamine some thought. Alkylation with methyl iodide will give the quaternaty ammonium salt but I found a reference where the quaternary methyl can be selectively removed by treatment with sodium borohydride in polar solvents. The reference is #2 in Organic Preparations & Procedures vol 12, 19809, no. 6 but it's available only via a pay wall. Pre DOI? The reference doesn't give the author's names. Don't have the original reference (#2). There are additional references here: https://www.tandfonline.com/doi/abs/10.1080/00397917408064096?src=recsys. NaBH4 is available in small amounts on eBay but not on Amazon.
JournalOrganic Preparations and Procedures International

The New Journal for Organic Synthesis


Volume 12, 1980 - Issue 6

Another Dow publication states that the NaBH4 only works with cyclic compounds involving quaternary carbons.

 

[JacksinPA]

Interesting paper on dealkylating quatenary ammonium salts using ethanolamines: https://www.thevespiary.org/rhodium/Rhodium/Vespiary/talk/index.php/topic,3255.0.html

 

[JacksinPA]

Interesting paper on dealkylating quatenary ammonium salts using ethanolamines: https://www.thevespiary.org/rhodium/Rhodium/Vespiary/talk/index.php/topic,3255.0.html

Ethanolamines are inexpensive but have their own unique properties: MEA smells like ammonia, DEA is carcinogenic, and TEA may be both carcinogenic & an allergen. It is also on the banned compound list for its potential to be a starting material for nitrogen mustard war agents.

 

[JacksinPA]

Ethanolamines are inexpensive but have their own unique properties: MEA smells like ammonia, DEA is carcinogenic, and TEA may be both carcinogenic & an allergen. It is also on the banned compound list for its potential to be a starting material for nitrogen mustard war agents.

Piperidine (b.p. 106 deg C.) might serve as an alternative to the ethanolamines. Unfortunately it is not available from either eBay or Amazon.

Also unfortunately, it is said to have an animal-type odor.

 

[Pomzazed]

Jacksin check your PM

 

[JacksinPA]

I just did but there was nothing new. BTW, I saved that article. Thanks!

 

[JacksinPA]

Since oral administration of DMT works best with a MAOI, I started looking for either simple RCs or naturally occurring compounds. I found tis interesting abstract:

https://www.ncbi.nlm.nih.gov/pubmed/3821373


Life Sci. 1987 Mar 16;40(11):1075-82.
Quinoline and quninaldine as naturally occurring inhibitors specific for type A monoamine oxidase.

Naoi M, Nagatsu T.
Abstract

Type A monoamine oxidase (MAO-A) in human placental mitochondria was competitively inhibited by naturally occurring substances, quinoline and quinaldine, using kynuramine as substrate. Quinoline had a higher affinity for MAO than kynuramine. MAO-A in human brain synaptosomal mitochondria was also competitively inhibited by quinoline, while type B MAO (MAO-B) was reversibly and non-competitively inhibited by quinoline. Quinoline inhibited MAO-A much more potently than MAO-B. Of several compounds structurally similar to quinoline, isoquinoline noncompetitively inhibited MAO-A and -B activity.

Isoquinoline is available from Amazon. It's description as far as flavor goes leaves a lot to be desired.

MAOI-A attacks serotonin, a structural analog of DMT.

https://www.livestrong.com/article/82970-common-herbs-mao-inhibitor-activity/

Common herbs that contain alkaloids that inhibit MAOI-A include Syrian Rue (Peganum harmala) which grows extensively in the Western U.S. and is not regulated. See
https://www.zamnesia.com/content/312-the-effects-of-syrian-rue