Hello to you all.
During the 1990 & early 2000s I was a researcher for a team of medicinal chemists. My job entailed finding all of the appropriate papers & patents. If another team was doing work that could be of use, I would contact said team directly. I am old enough to remember ChemOffice being introduced (and how amazing it was). Then Lipinski's rules of five (RO5) was formally recognised and Crossfire (the precursor of Reaxys) was brought in (and was even more amazing. Anybody who is old enough to remember 'Chemical Abstracts' (CVAS) will understand what I mean.
www.abebooks.co.uk
Part of my work was in translating papers & patents into English or Dutch. I used a number of utilities & several technical dictionaries and we employed people on a per-project basis to check said translation. I do not claim that the translations were great BUT the external translator would ensure that the KEY elements of papers & patents were translated perfectly. Overall it saved us a lot of money.
From 2003 until 2011 I helped Linnell Publications (a HR agency) and wrote a number of articles that were published in various broadsheet newspapers. They were generally concerning new drugs-of-abuse were becoming increasingly popular. While doctors were enamoured of Ultram (tramadol) whereas I recognised that it's SNRI dose-response curve meant that it was much more toxic than an equipotent dose of codeine, for example. I also noted that out that Lyrica (pregabalin) produced physical dependence in animal models and that ALL GABA genic PAMs similarly produced physical dependence but animal models have little value in testing psychological addiction. The FIRST experiment to test addictions was as recent as 2013 (The Development of a Preference for Cocaine over Food Identifies Individual Rats with Addiction-Like Behaviors -https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079465) and this kind of testing is NOT required to obtain a licence to market a new drug.
From 2012 until 2014 I helped to develop a large number of intermediate building blocks for commercial sales. After all, it's often cheaper to spent $600/g of a material than to go through the extra 6 steps in it's synthesis. We kept a close track on what was sold and ensured that we always had a ready supply. The number of building blocks stretched to over 27000 compounds. I hasten to add that the 27 full-time staff that the company.
We discovered that the MOST profitable way to run such a service is to send the potential NDA (sometimes they sent their own NDA - a belt & braces approach. That done, we would OFTEN find a much more efficient synthetic pathway and tell the customer. We would not disclose the route but we had 1 chemist whose job it was to perform the syntheses aiming at a yield of 5 grams. He kept copious lab-notes. What we WOULD do is to offer either to make the chemical ourselves If a customer needed more than the 1Kg scale our lab & labware limited us to, we would always pass on the customer to The Mole Chemical Corporation which is run by a man we call 'The Mad Major'. He was in the British army, specifically the RAOC & was an ATO. Put simply, it was a bomb disposal expert. He's also a wonderful chap.
m.chemicalbook.com
His ads are very, very low key but just as an example, he sells 100-200 Kg of 2-phenylnitropropene (CAS 705-60-2/SMILESO=N(=O)C(\C)=C/c1ccccc1) every week. It's quite legal BUT the only commercial use of this chemical is in the production of Adderal and generic IR dexamphetamine,
If I may OT a little more, I am truly shocked by the fact that a whole generation of 'cooks' have been taught the (pseudo)ephedrine ---> (S) methamphetamine rpute. The US government seems to have been surprisingly efficient in making (pseudo)ephedrine too costly, too inconvenient and too complicated to acquire as a precursor and so phenyl-2-propanone (P2P) has become the most common route. While I am impressed by the DEAs efforts, I see that L-PAC* is very cheap (produced at scale in bioreactors). OK, so it's 1 extra step BUT the price is so low, I cannot imagine it not becoming the standard synthetic pathway. There are several (pseudo)ephedrine related chemicals that can be made from L-PAC so the people actually providing these materials are not breaking any national or international laws.
Lastly, I have a feeling that L-PAC can, in a single step, produce 4-MAR. I haven't found a route yet but I have noted a rule-of-thumb which states that a 'cook' can only make a product that uses a maximum of 2 steps & 2 workups. A decent chemist can reliably produce a compound that requires 4 steps and 4 workups assuming that the yield of eacvh step is high. After all, if each step has a yield of 50%, four of them will only produce an overall yield of 6.25%. Well, OK, I suppose sociopaths who are prepared to make p-F OHMefentanyl and possess chiral precursors would still profit given that they are able to make 3R,4S,βS-p-F-ohmefentanyl which is ovcer 30,000 x more potent than morphine and even if the 1Kg (rounding up here) only returns 62g of product, that's still 930Kg of uncut (heroin).
I AM fascinated by the science behind psychoactivce drugs but I have witnessed the harm they can cause - splitting up families, the breakdown of relationships, crime, overdoses and infection by blood-borne diseases. More recently I've had 3 friends die as the direct result of drug consumption and even worse, my friends Shelby (AKA Paupiere de Quincy AKA Dequincey Jynxie & Brian. They were both talented artists making a decent livcing. Unbeknownst to them, the house they rented had previously been occupied by a mid-level drug dealer. One night someone broke in seeking a 'stash'. On failing to find one and not wishing for their to be witnesses, Paupie & Brian were bound head & foot, tortured and murdered by a single shot to the back of the neck.
So I have experience of being surrounded by wonderful and talented medicinal chemists AND to have seen the other side of the coin where life is cheap.
I'm sorry this ended up so long. I'm still getting over loosing Shelby.
During the 1990 & early 2000s I was a researcher for a team of medicinal chemists. My job entailed finding all of the appropriate papers & patents. If another team was doing work that could be of use, I would contact said team directly. I am old enough to remember ChemOffice being introduced (and how amazing it was). Then Lipinski's rules of five (RO5) was formally recognised and Crossfire (the precursor of Reaxys) was brought in (and was even more amazing. Anybody who is old enough to remember 'Chemical Abstracts' (CVAS) will understand what I mean.
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Part of my work was in translating papers & patents into English or Dutch. I used a number of utilities & several technical dictionaries and we employed people on a per-project basis to check said translation. I do not claim that the translations were great BUT the external translator would ensure that the KEY elements of papers & patents were translated perfectly. Overall it saved us a lot of money.
From 2003 until 2011 I helped Linnell Publications (a HR agency) and wrote a number of articles that were published in various broadsheet newspapers. They were generally concerning new drugs-of-abuse were becoming increasingly popular. While doctors were enamoured of Ultram (tramadol) whereas I recognised that it's SNRI dose-response curve meant that it was much more toxic than an equipotent dose of codeine, for example. I also noted that out that Lyrica (pregabalin) produced physical dependence in animal models and that ALL GABA genic PAMs similarly produced physical dependence but animal models have little value in testing psychological addiction. The FIRST experiment to test addictions was as recent as 2013 (The Development of a Preference for Cocaine over Food Identifies Individual Rats with Addiction-Like Behaviors -https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079465) and this kind of testing is NOT required to obtain a licence to market a new drug.
From 2012 until 2014 I helped to develop a large number of intermediate building blocks for commercial sales. After all, it's often cheaper to spent $600/g of a material than to go through the extra 6 steps in it's synthesis. We kept a close track on what was sold and ensured that we always had a ready supply. The number of building blocks stretched to over 27000 compounds. I hasten to add that the 27 full-time staff that the company.
We discovered that the MOST profitable way to run such a service is to send the potential NDA (sometimes they sent their own NDA - a belt & braces approach. That done, we would OFTEN find a much more efficient synthetic pathway and tell the customer. We would not disclose the route but we had 1 chemist whose job it was to perform the syntheses aiming at a yield of 5 grams. He kept copious lab-notes. What we WOULD do is to offer either to make the chemical ourselves If a customer needed more than the 1Kg scale our lab & labware limited us to, we would always pass on the customer to The Mole Chemical Corporation which is run by a man we call 'The Mad Major'. He was in the British army, specifically the RAOC & was an ATO. Put simply, it was a bomb disposal expert. He's also a wonderful chap.
Mole Chemical Corporation Product Catalog_Page 4_Chemicalbook
His ads are very, very low key but just as an example, he sells 100-200 Kg of 2-phenylnitropropene (CAS 705-60-2/SMILESO=N(=O)C(\C)=C/c1ccccc1) every week. It's quite legal BUT the only commercial use of this chemical is in the production of Adderal and generic IR dexamphetamine,
If I may OT a little more, I am truly shocked by the fact that a whole generation of 'cooks' have been taught the (pseudo)ephedrine ---> (S) methamphetamine rpute. The US government seems to have been surprisingly efficient in making (pseudo)ephedrine too costly, too inconvenient and too complicated to acquire as a precursor and so phenyl-2-propanone (P2P) has become the most common route. While I am impressed by the DEAs efforts, I see that L-PAC* is very cheap (produced at scale in bioreactors). OK, so it's 1 extra step BUT the price is so low, I cannot imagine it not becoming the standard synthetic pathway. There are several (pseudo)ephedrine related chemicals that can be made from L-PAC so the people actually providing these materials are not breaking any national or international laws.
Lastly, I have a feeling that L-PAC can, in a single step, produce 4-MAR. I haven't found a route yet but I have noted a rule-of-thumb which states that a 'cook' can only make a product that uses a maximum of 2 steps & 2 workups. A decent chemist can reliably produce a compound that requires 4 steps and 4 workups assuming that the yield of eacvh step is high. After all, if each step has a yield of 50%, four of them will only produce an overall yield of 6.25%. Well, OK, I suppose sociopaths who are prepared to make p-F OHMefentanyl and possess chiral precursors would still profit given that they are able to make 3R,4S,βS-p-F-ohmefentanyl which is ovcer 30,000 x more potent than morphine and even if the 1Kg (rounding up here) only returns 62g of product, that's still 930Kg of uncut (heroin).
I AM fascinated by the science behind psychoactivce drugs but I have witnessed the harm they can cause - splitting up families, the breakdown of relationships, crime, overdoses and infection by blood-borne diseases. More recently I've had 3 friends die as the direct result of drug consumption and even worse, my friends Shelby (AKA Paupiere de Quincy AKA Dequincey Jynxie & Brian. They were both talented artists making a decent livcing. Unbeknownst to them, the house they rented had previously been occupied by a mid-level drug dealer. One night someone broke in seeking a 'stash'. On failing to find one and not wishing for their to be witnesses, Paupie & Brian were bound head & foot, tortured and murdered by a single shot to the back of the neck.
So I have experience of being surrounded by wonderful and talented medicinal chemists AND to have seen the other side of the coin where life is cheap.
I'm sorry this ended up so long. I'm still getting over loosing Shelby.
. Very interesting career you have had.