Need to let loose a primal scream without collecting footnotes first? Have a sneer percolating in your system but not enough time/energy to make a whole post about it? Go forth and be mid: Welcome to the Stubsack, your first port of call for learning fresh Awful youāll near-instantly regret.
Any awful.systems sub may be subsneered in this subthread, techtakes or no.
If your sneer seems higher quality than you thought, feel free to cutānāpaste it into its own post ā thereās no quota for posting and the bar really isnāt that high.
The post Xitter web has spawned soo many āesotericā right wing freaks, but thereās no appropriate sneer-space for them. Iām talking redscare-ish, reality challenged āculture criticsā who write about everything but understand nothing. Iām talking about reply-guys who make the same 6 tweets about the same 3 subjects. Theyāre inescapable at this point, yet I donāt see them mocked (as much as they should be)
Like, there was one dude a while back who insisted that women couldnāt be surgeons because they didnāt believe in the moon or in stars? I think each and every one of these guys is uniquely fucked up and if I canāt escape them, I would love to sneer at them.
(Semi-obligatory thanks to @dgerard for starting this.)
I read through this with my wife who actually did a whole course of organic chemistry, pre-med, etc. Her reaction to your criticisms was largely āof course you would have to do that and thatād be a pain in the ass but itās definitely doable.ā And I feel like thatās probably true but at the same time as a reasonably smart dude this is the first time Iāve heard the majority of these words.
It feels like theyāre reacting to the same tendency in tech culture that Iāve complained about before where specialized knowledge and domain expertise are treated like arcane revelations from beyond. Itās not that your average person is incapable of understanding or going through the relevant processes; Cs ,as the saying goes, get degrees and Iām sure many of the labs actually doing this work at scale are staffed largely by those C students. But itās also worth acknowledging that there is a level of investment in time and resources required to actually do it and this kind of āyou have nothing to lose but your pharmacological chainsā rhetoric is dramatically underselling how difficult those processes are and how bad the consequences can be if you screw it up. Anyone who wants to try should first read The Iliad, the Oedipus cycle, and at least one other epic-sized meditation on hubris. And the once youāve forged ahead read the relevant books on actually following the process for the love of God.
of course you can make it work but itās more expensive and harder than normal commercial synthesis. with such limited analytical methods you might not even be able to tell that something went wrong (melting points can be completely fucked up by traces of solvent, same with IR) naloxone is actually a nice example of how you can design synthesis in order to make your life easier, in terms of purification at least. one of commercial syntheses looks like this
anyway thatās what i found in one chinese patent (CN104230945A). they start from oxycodone, which they make from thebaine, which they donāt have to make because itās a natural product. thereās a very useful purification technique, column chromatography, that works like this: you take a tube, fill it with silicagel, then pour hexane through it, then put your compound on top of that silicagel column. silicagel is polar, and the more polar compound is, the stronger it is bound to it. so now in order to get your pure compound you wash this column with increasingly polar solvents, and this way you can recover various compounds in order from least polar to most. this allows you to get pure compounds most of the time
now, small changes in or near polar groups mean that polarity changes little. in particular, we can ignore for five minutes all these hydroxyls and just focus on amine because itās the most polar part and any changes at other groups make polarity change in the same way anyway. step 2 is von braun degradation, and it removes methyl and turns amine into amide. this amide is very likely to have much lower polarity than starting product and so it can be easily separated on column. here specifically, itās no longer basic so unreacted acetyloxycodone can be just washed away with acid extraction, which is good for both low tech and large scale. step 3 is hydrolysis, which gives us amine back, which again gives more polar product which means again that separation is easy. if some acetyloxycodone was left there, it would give very similar compound, just with that N-methyl left and separating it would be pretty hard. this here is especially important as N-methyl and N-allyl compounds have opposite effects
that weird synthesis with burgess reagent and everything else also allows for separation of these unreacted starting materials, but this requires column chromatography in the middle. if you skip it, maybe itāll turn out alright or maybe you just fucked up for the last time. maybe mCPBA was old, or maybe burgess reagent or THF was wet, or any variety of random bullshit that someone inexperienced would not even register. and this is only one point that brings us to point 2: that jarduino is really juicero of backyard chemistry. to begin, you need dry solvents, and this is something you should do yourself if you want it to be done right. this means you need to reflux THF with drying agent of your choice, then distill it away to clean dry bottle, fill it with argon, ideally add molecular sieves and tape it shut. then you have to reflux something, this requires all glass flask because that 3d-printed head will melt under these conditions. at some point you also need sep funnel and rotovap and column, and so on and so on and it turns out that you already have all glassware to do it all the normal way and jarduino isnāt even needed for anything. (also i donāt understand their choice of peristaltic pumps, as they already put everything in syringes, this means that you can just use syringe pumps and use normal medical long needles for piping of sorts. itās very chemically resistant as long as plungers arenāt rubber, which their demos had for some weird reason)
this is closer to the synthesis i thought they were using
if you swap oripavine for oxymorphone and cyclopropylmethyl bromide for allyl bromide, you should get naloxone, probably, in 2 steps.this doesnāt work keeping cyclopropylmethyl bromide and using oxymorphone gets you naltrexone which also works as antagonist and even slightly more potent one, itās from this paper https://cdnsciencepub.com/doi/10.1139/cjc-2014-0552then there are all the sterility requirements, as they want to make injectables in garage. iām not pharmacist or biologist, but i expect it would be a bit harder to make it reliably and repeatably than what they make it look like. i take that your wife is a medical professional so if she weighed in on that, that would be nice
also, part of their advice is to just eyeball powder as a part of identification. this is a bad idea because how stuff looks like and behaves can change depending on humidity, traces of solvents if any, and ambient temperature, especially for low melting solids, and crystal habit can vary from batch to batch anyway and itās not a reliable indicator of anything
Unfortunately actually working in bio/med didnāt go well despite training for it aggressively and working her ass off given that she graduated at the perfect time to compete for entry-level positions with recently laid-off people with 5+ years of experience. Between that and chronic illness in the family will all the associated experience with the failings of our medical system Iām actually pretty sympathetic to the biohackers from a purely ideological perspective, but these people are just begging for a disaster.
Beyond reading through and enthusiastically agreeing with everything you had, she did say that if youāre working on anything consumable or injectable using 3D printed parts at all is going to be a red flag. Your first two pieces of equipment should be an autoclave and a fume hood, at which point youāre better off working with all glass for durability and not melting reasons. Making your work space actually sterile and sufficiently free of contaminants to do any of this jnt be first place is also going to be a pain, require a lot of tape and curtains and the like, and probably not work as well as youād want.
Also even working in a proper university lab with a fume hood and climate controls you still get sufficiently different results that the mk1 eyeball is utterly insufficient for identification. Youāll learn worse than nothing.
I keep having to remind a couple of my friends who got 3D printers for themselves as gifts that 3D printed parts arenāt ever food safe, much less whatever standardās required to make safe injectables. specifically, bacteria likes to hide inside the layer lines on FDM parts, and resin parts are made of a material that shouldnāt be ingested or introduced into your bloodstream
on chemistry side, i guess you can wing it a bit and not strictly require fume hood in low population density area. not having rotovap, at best with appendages (chiller + chemical resistant vacuum pump, aspirator gives limited capability) makes all but simplest syntheses deeply unserious to impossible especially if you want to do some analysis later. especially if itās IR and melting point because solvents fuck up both