this post was submitted on 16 Sep 2024
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Big brain tech dude got yet another clueless take over at HackerNews etc? Here's the place to vent. Orange site, VC foolishness, all welcome.

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[–] [email protected] 0 points 3 months ago* (last edited 3 months ago) (1 children)

right, so let's start with equipment. instead of using lab-scale techniques with lab-scale equipment, they instead decided to make an industrial-type reactor but tiny. so for a thing that stirs and heats your reaction mix they came up with arduino-powered jars that cost all in all $300-500. you know what does this job? a hotplate-magnetic stirrer combo with external thermometer that you can get on amazon for $70ish, with some associated glassware that still will be cheaper than $300 total, won't leach plasticizers and that you can actually clean up thoroughly. if you're looking for case of coder mindset where every problem can be solved with iot and 3dprinting, it's there. that thing only really allows purification by extraction and crystallization, but this is straight up not enough for some cases. maybe they're limiting their syntheses to cases where it is enough. sometimes you need to run distillation, if it's something other than solvent this means vacuum pump ($2k ballpark) with dry ice trap (that has to be fused quartz and not normal glass) and dry ice. sometimes you need to run chromatographic column, that alone is easy if you know what you're doing but it requires a lot of solvent that would be ideally recycled because there's a lot of solvent involved (100x mass of compound to be purified is on lower end) (honeywell doesn't want you to know this but recycled solvent is free you can do it in-house. i recycled 1500L). then you need equipment to evaporate that solvent (rotovap) and recycle it. like derek lowe said, it's a lot of like trying to make your own aluminum foil

and then there's entire waste management of it all, and there will be a lot of waste that you just can't flush down the drain

another problem is that they expect anyone to be tied to this rube goldberg model reactor and don't provide instructions in human readable form, but only as instructions for that contraption, and even that only through chatbot (??) if you can pull something let me know. (they have something better than machine generated free association right? as in, something they have tested. i don't expect orgsyn.org level work where they repeat all procedures they publish, but at least something grounded in reality)

like you said there's zero quality control and options for purification are extremely limited, this alone will get people killed. some of their testing was outsourced, and there are some ancient methods of determining what you've got based on things like melting point, but this is critically sensitive to fucking up due to not knowing what you're doing. but this won't tell you what it is, it only allows you to compare your result to someone's else result to check if they match. i don't know how likely in this case would be that fucking up synthesis will get patient killed, but in their previous one where they tried to cook naloxone there was a way to fuck up synthesis that would give compound with opposite activity to what was intended (oxymorphone).

regarding sofosbuvir. it's fluorinated, which means they either

  1. handled xtalfluor-type reagent and hydrogen fluoride-triethylamine complex in their garage, which will get people killed if they try to make it at home without necessary preparation like good fume hood and PPE and knowing what do to in case of accident, and requires teflon or poylethylene containers because this thing corrodes glass and expensive reagent disappears, or
  2. bought fluorinated building block. due to quirk of stereochemistry in this case it's easier to fluorinate that position after nucleobase is already installed, which means they just probably bought right half of sofosbuvir (as drawn on wikipedia) and tacked on the rest (which looks easy but still requires rather spicy chemicals). i don't think their supply will be cheap then, but if it works then their stated goal of bypassing patent-based profit extractors could work if (load bearing if) nothing goes wrong along the way, but i have doubts as of how sustainable will this get, or
  3. they're just bluffing

and this is all forgetting about that sofosbuvir is used in combination therapy, where all the other drugs come from

the other drugs are also patented and just from looking at them it seems to me that these require a bit more specialized starting materials and a few steps that involve palladium couplings

synthesis-prediction software is an alleged thing that will sometimes work, i personally never did, but if you do use it, it's critically important to know what you just have cooked because these outputs are predictions, not procedures. in this case point is moot because they just can replicate what is in patents, as patents describe something that already works, even if some details are missing

there are degrees to it. their abortion cards from what i understand just repurpose veterinarian misoprostol, which has similar if not the same requirements for purity and such and because it's also used in humans, i won't be surprised if it (as in, API) rolls off the same production line. but here, they don't cook anything so there's less room to fuck up. this is also not golden standard on how pharmaceutical abortion can be done now, but it's available and it's basically unregulated which i suspect was the entire point

single sane take from hn that is grayed out for some reason. something like quarter of discussion involves nootropics

This looks more like a libertarian nightmare than an anarchist dream. I couldn't care less what you inject your body with, and will always support open science, but this is no solution to the USA's disastrous healthcare system.

The real "right to repair your body" necessarily involves a socialized healthcare system, like in the rest of the West.

[–] [email protected] 0 points 3 months ago (1 children)

Deep dive into complex chemistry may be the most important thing in this thread. The bullshitters need more pushback like this, even though the effort involved means it can't happen nearly as often as the bullshit. Thank you.

[–] [email protected] 0 points 3 months ago

if you want a deep dive, show me a procedure this thing is supposed to be using because i found nothing serious

also just noticed that their warrant canary does not include proof of date like news snippet and is not signed