Tetrahydrogestinone AKA'The Clear' (THG)

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Bluelighter
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Apr 12, 2013
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Hi,
I just wondered if this compound, the most potent anabolic steroid (AFAIK) is available. I know that RU-2309 was developed and used by the Turkish Olympic weightlifting team (who all got banned) and that is just a slight modification to THG. It would be synthetically complex to make but they wanted as close to THG as possible it seems. BALCO was not exactly a group of able chemists - THG is a 1-step synthesis although it is now a controlled drug. Of course, the hemi-acetal derivative IS legal so I'm wondering if that is turning up.

THG = (8S,13S,14S,17S)-13,17-diethyl-17-hydroxy-1,2,6,7,8,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
THG (methyl) Hemiacetal = (8S,13S,14S,17S)-13,17-diethyl-17-hydroxy-1,2,6,7,8,14,15,16-octahydrocyclopentaphenanthren-2-ol

The ethyl hemiacetal avoids the tiny traces of methanol formed by hydrolysis to active (but truly TING amounts) and the acetal can be with any alcohol(s) or cyclic using ethylene glycol or propylene glycol or indeed any diol that doesn't cause too much ring-strain or alters kinetic by lower solubility. Ketone<->enol tautomerism offers unsaturated esters, another gamut of options.

In short, there is a panopticon of possible legal analogues is well understood but it doesn't look like technical knowhow or indeed interest is involved with the production of novel steroids. They are of course not without their own risks and I only highlight this on the basis that people misusing steroids meant for animals (!!!) and at least this offers a known compound. The reason I specifically mentioned the methyl hemiacetal is that it is possible to go from gestinone --> THG methyl hemiacetal without raw THG turning up in the solution thus nobody is in breach of UK law (AFAIK) apart from unlicensed pharmaceutical so strictly, this is a reference ligand because forming the methyl hemiacetal of an unknown can use a THG-hemiacetal as a reference compound i.e. it is of value in detecting the illegal use for PED.

I wish to make it clear that while 1-step may seem 'do-able', it does use a pyrophoric reagent and a flammable solvent. Get it wrong and it could cost you your home, your family and/or your life. I am not an expert on steroids but I do believe that informed consent is only possible if the compound is correctly identified. AFAIK THG was given sublingually dissolved in a solvent. I don't know how stable the (hemi)acetals & unsaturated esters are. The former is NOT technically an ester so MoDA doesn't cover it and since the unsaturated esters dehydrate the molecule (loses a H2O) the law would see it as an ester of a non-controlled item.

Don't break the law. Don't do stupid things. Don't harm anyone.
 
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It's certainly potent at suppressing the HPTA - significantly moreso than progesterone, which isn't a good thing at all and was reputedly rather liver toxic with a lot of unpleasant sides.

It was also never renowned for having particularly exceptional anabolic effects. It was used merely because at that time it wasn't detectable. Other options on the market for bodybuilders (eg tren) do more with fewer side effects.

Back in 2003 when the scandal broke, I remember there being a momentary interest in it by bodybuilders, and probably a few 'fake' products claiming to be thg, but by 2005 that had evaporated and I haven't seen it in over a decade.
 
Indulge me - what anabolics are people using? I have literally no idea. I keep reading of trenbolone being diverted from animal medications which seems a bit risky. I only mentioned it on the off-chance that it would reduce harm.
 
Tren was once upon a time extracted from pellets - some of my nicest early homebrews came from that route, and not at all risky if done correctly.

But nowadays few would bother as there's a ready supply of powders from China, India and other countries of every anabolic you could wish for.
 
I appreciate that the sources have changed but I'm more interested in what steroids are actually in use. I mean commonly in use. I have read (long ago) how people chose them for increased endurance, anaerobic exercise, bulk forming and so forth. It sounded rather involved and I really don't know if power lifters use one set while marathon runners use others. It's not an area I have studied deeply although I do occasionally co-respond with Dr. Daniel Lednicer who literally wrote the book on the subject (Steroid Chemistry at a Glance) which has the most fantastic dedication in any book in any language in the history of the world.

Dr. Lednicer is a true genius, a gentleman and a scholar. He wouldn't be happy that his work went into non-medical steroid use but on the other hand, I would argue that he not only founded the field but he also carried out all of the studies and trials so he REALLY knows what goes on and so we can take his hard-earned knowledge to reduce harm.

I know things like 2,4-dinitrophenol and blood-doping are far more hazardous (I've seen an athlete drop dead on a flight because he didn't take enough blood thinners) but informed consent requires people to be informed.
 
Testosterone
Boldenone
Nandrolone
Trenbolone
Primobolan
D-bol
Anadrol
Winstrol

I'd say those are the most used.
 
Testosterone
Boldenone
Nandrolone
Trenbolone
Primobolan
D-bol
Anadrol
Winstrol

I'd say those are the most used.

Yep those are the staples. Throw in halotestin and Masteron as well for contest prep.
 
Firstly, thank you for your help. I'm going to get a large training set & run CHARMM to figure out the 3D QSAR. Some random notes:

I note that the A-ring has a 3-keto moiety (a C=O) or bioisostere.
-double-bonds (-C=C-) are present on the A, B & C rings to make the scaffold planer (flat) and possibly as binding sites themselves.
-A chiral tertiary alcohol (or ester of) & methyl @ 17 in all.
-Chiral methyl groups are common at the 5 & 7 position (space-filling? Increasing rigidity? Increasing affinity?).
-Vestages of an E-ring increases activity.
-A methyl or ethyl @ 18 (CD junction) increases activity.
-Looking at THG, replacing the 17 methyl with an ethyl increases activity.
-THG has a double-bond at the junctions of the AB,BC & CD rings making it totally planer.
-The ketone prevents the body from hydroxylating the 3 position (which can then form an ester with gluconic acid and be removed by the kidneys).
-Ethyl groups are more readily oxidized to hydroxyls (CH --> C-OH).
-The body also hydroxylates the 11 position.
-Fluorines are added at ring junctions to increase rigidity.
-It seems that hydroxylation @ 11 is the preferred metabolic pathway.
-Prodrugs are mostly long-chain esters that the body hydrolizes so duration can be 'tuned'.

I note that a number of neuroactive steroids are known. Many modulate GABAa (so some benzo-like action). I cannot put my finger on it but at least 1 steroid is an opioid. If memory serves it's a fluoropropanate ester. Cyproterone is an example.

The action of steroids is really interesting to me. I'm wondering if (CNS mediated) analgesia and sedation/hypnotic activity can be added to anabolics. I can now glimpse the complexity of design and luckily I co-respond with Dr. Daniel Lednicer who wrote the landmark book 'Steroid Chemistry at a Glance'. The dedication is 'To libido, without which this book would be neither useful or possible'. It is very, very subtle. I now realize that BALCO was no different to any other clandestine drug manufacturer. The simple axiom 'a straight line is the shortest path between 2 points' in action. Triple bonds (-C≡C-) seem to occur only in (semi) synthetic steroids and ketone moities on the D-ring seem to be associated with female hormones. Gestinone was used to treat entopic pregnancies and the guy at BALCO just spotted that reducing the triple bond to a single bond made it into an anabolic showing how subtle things are. The A-ring being aromatic is interesting as it is both planer and stable. If a methyl ether will substitute for a ketone (i.e. only the lone-pair is important, it isn't forming an imine with an amine). It hasn't been tried and I don't know if it's simply not useful or possibly it's too synthetically difficult. Ethers are prodrugs but aromatic ethers may not be.

I asked if THG was the most potent because the entire Turkish wrestling team were thrown out of the Olympics for using RU-2309 and/or RU-1881 which differ only by one ethyl being changed to a methyl. They all come from the French drug development company Roussel-Uclaf hence the RU prefix. The company was a startup JUST developing steroids and in 13 years over 30000 were listed! All were developed between 1980 & 1993 and considering they published frequently, once a chemist knows where to look, the data-set will be huge. Of course, at the time computer-aided 3D QSAR software didn't exist but it would be an interesting (if lengthy) process to input ALL of the compounds with affinity & metabolic data to find the candidates for very specific criteria. It would HAVE to support OCR or some poor intern will lose the plot. I suppose purpose-made software that recognizes the 4-5 ring systems, the double & triple bonds and the presence of other elements (N,O,F,Cl mostly).

Now I see why so much information is needed to minimize risk to users. I see quite a lot of that Turkish team have suffered serious health problems (including death). A friend was a semi-pro cyclist (she thought nothing of cycling 40 miles to visit me for 1 hour) and told me all sorts of stories CC blood-doping and how every decade brings a new class of drug. Stimulants like amphetamine, methylphenidate, phenmetrazine & levophacetoperane. The last one of these is of particular interest because while 1 of the 4 isomers is a stimulant, at least one of the others had sedative-like activity (although I suspect that it's actually mediated by opiate receptor affinity). There is a joke term used by medicinal chemists using animal models, 'ratatonia'. Give a rat speed, it freezes. Give it a benzo, an opioid, cocaine, nicotine and even caffeine and catatonia results... one reason why animal models fail to identify useful activity. I have always sought to use the very legal minimum of animals and then signed myself up for the stage 1 trials. If it's going to harm someone, that someone should be me.

I am going to read a lot more but for now, once more, thank you.

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