Total Synthesis of Lysergic Acid (LSD Precursor): Retrosynthesis & Mechanisms (Hofmann, Woodward)

[@totalsynthesis]

Feel free to check out my other videos in case you're interested in chemistry and science! I also plan on sharing smaller, bite-sized insights on instagram: instagram.com/totalsynthesis_official/

[@fukpoeslaw3613]

Would bromadol be easy enough to make?

[@brettmoore3194]

Why synthesize when nature makes it so easily, while sequesting carbon, extracting minerals while also making sugars,starches and cellulose. A inventor would be proud to have a product perform so well

[@fukpoeslaw3613]

@@brettmoore3194 men improves on nature's medical drugs by 10, 100, 1000 times.

[@brettmoore3194]

@@fukpoeslaw3613 sorry but you consider a product that doesn't cause unwanted effects from a product that say it does this but also has these adverse reactions .... How is that improved. Father of medicine said it best let food be the medicine.

[@brettmoore3194]

@@fukpoeslaw3613 sound kinda pompous to say man can improve on perfection

[@viktorprypoten5233]

man, chemistry really did peak in the 50s and 60s

[@kennethstreet7868]

@Joe Alexander Mandelbrot, no space

[@cvspvr]

sounds like something tom from explosions and fire would say

[@viktorprypoten5233]

@@cvspvr precisely the shitpost

[@Swagtildawn]

@Joe Alexander What about it? There have been textbooks written on the subject in length. Not that they explain everything, but what are you referring to exactly?

[@skm9420]

It's all gone yellow

[@lumpygasinavacuum8449]

the world needs mass amounts of bike day chemicals. humanity needs more chemists

[@bergenmatthew]

No we need the chemicals unregulated

[@bergenmatthew]

So much of thestuff to synthesize lsd is regulated

[@Yazyk]

@@bergenmatthew there are ways around this if you're are looking for ways. We need more people who take initiative.

[@bergenmatthew]

@@Yazyk growing ergot doesnt seem fun to me.

[@Greatwealthgentleman]

Yes we need both, too bad that organic chemistry is so complicated otherwise we would have more people making it

[@edwardarruda7215]

I'm a retired R&D chemist and find this a nice refresher.

[@SAVEmeFROMtheANTS]

Still looking for 'work'? ;)

[@Pillowpetlover]

heisenburg

[@AltarParssoy]

ohno process too far fetched to my eyes, don't you think?

[@jackmariner]

How would one go about isolating LSA from morning glory seeds, and then turn it into LSD? Not asking for me or a friend just curious

[@electronium6378]

say my name

[@trevortyleris]

Straight called out for watching this while tripping. You earned a like.

[@prostrongmanzack]

As a chemist in industry, this is fantastically interesting. I found the depth of explanation of each time period most interesting, it is fun to think about chemists not so concerned with PPE 🤣🙏

[@nana-rs8en]

Some still don't, I always hated being forced to use it when I was learning.

[@FerociousPancake888]

Dealing with cyanide? Just have a smoke!

[@tylersmith1749]

The best chemical ever synthesized. Not meant for daily or even monthly consumption but for when you need a new perspective.

[@yourface13able]

"..Or some random bloke just tripping acid, I hope you enjoy this video" Me on acid watching this video: ¤_◇ I am chemical

[@ScheveSneeuwSchuifSchep]

@Jay Hamrz uhh where do you live? It's pretty easy to get here lol

[@ScheveSneeuwSchuifSchep]

@Jay Hamrz you can actually send your drugs to a test lab for free where I live to test if your dealer supplied you with what they said they sold you

[@ScheveSneeuwSchuifSchep]

@Jay Hamrz yes you can buy test kits on Amazon but I refuse to buy anything on Amazon. Also I'd rather have it tested by a certified lab chemist which is legal and free in my country. Piss off, just because you live in a different country with different supply it doesn't mean that your situation is true for the entire world.

[@borat1]

@@ScheveSneeuwSchuifSchep man what country do you live in? I want to try acid but I’m kinda scared of the fake stuff.

[@kmit9191]

@@borat1 In Austria for example his Situation could be true.

[@ivanmassimo4769]

high quality video.. no music no bullshit... it's hard nowadays to find such seriousness in youtube.

[@ronaldpeanut779]

Excellent. Wish I had a teacher like you when I started grad school in 1987.

[@elit3chemist958]

keep up the good work buddy, honestly this is what i want to see on youtube , will support ur channel :)

[@totalsynthesis]

Thanks mate. I have no time at all to make a video this weekend and coming week but will try to make a new one by next Sunday.

[@BushyHairedStranger]

Total Synthesis Garbrecth synthesis video? It would be great to have the resource variety of different synthesis available on KZbin. Appreciate what you’ve provided here alone.

[@juanbisceglia8322]

Watching the 2011 synthesis I can't help stare in awe at our predecessors ingenuity. Beautiful video!

[@abhijitha8150]

Enjoyed the video. I feel stereoselectivity is of paramount importance while discussing total synthesis in this day and age and maybe you can ask your viewers who find it difficult to skip to another point in the video. This is a very good initiative and I sincerely hope you will inspire many thousands of students to pursue Organic chemistry.

[@donbredorouso2787]

I took ochem to the 400 level, and after 8 years, I can recognize some of what you are saying. I understand the drawings. I dont know every or any of the reaction type or mechanisms behind them. It would be cool if you had the molecules move around and have arrows moving around to show the reaction. I like the history aspect, old, middle, new. I think it was great, I will watch more.

[@hugostiglitz6823]

So what you're saying after 8 years even attempting lsd synthesis is almost impossible to the layman 😄

[@donbredorouso2787]

@@hugostiglitz6823 but we all dream of doing it.... i thought about it today....

[@BrasilKid]

@@donbredorouso2787no way can it be impossible think PyBOP mechanics

[@lumiii_-]

Happy I found this. I want to study the effects of LSD analogs, specifically AL-LAD, and try to understand why differences and similarities may occur between them. Research so far has been...groovy ✌

[@jedwalsh5308]

Me being an A level student who has only just done Friedel-Crafts reactions thinking I would have a chance to understand the mechanisms.

[@jg_5082]

Bro same 😂 still cool though

[@Alexei_topalov]

Yeah I remember taking one look at this synthesis as an A level student and just being like ‘nope.’

[@jedwalsh5308]

@@Alexei_topalov so much still to learn 😂

[@ThaFill]

I really like how you explain the history, give some anecdotes and cover the modern as well as the old approaches. This is something that fascinates me the most, in terms of green chemistry and upscaling! Thanks for the heads up on reddit and the amazing content! Keep going!

[@williamguthrie8507]

This video is kind of old now but as an undergrad chemistry student, this video was perfectly suited for my knowledge level, love the video.

[@totalsynthesis]

Thank you! I hope you enjoy the new ones as well

[@Rayselddiaz]

Complicated and history driven videos are a delight.

[@n.thatte7698]

I really enjoyed the clarity of explanation: the video engaged well with the philosophy of why certain steps are taken. Good job! I thought the difficulty level was spot-on too!

[@jimmysjamin1]

I love the idea of helping people displaying symptoms of Altzhimers and other challenging conditions very well done and easy to understand lecture.

[@TajwarC]

Came from reddit - found the retrosynthesis very well suited to my knowledge level as an undergraduate. I can see some of the sharper college students (17/18 year olds) keeping up too if the reactions or mechanisms are named during the forward synthesis. Keep it up!

[@TheBen9701]

I have no idea on half of the content of this video, but your voice is soothing and the history is interesting!

[@koukouzee2923]

I find it fascinating synthesizing complex drugs like this

[@seancady4570]

Random bloke part made smile. Thanks for the shout out

[@totalsynthesis]

I knew you would watch this after 6 years!

[@Richard_allrich]

Well that's some high level chemistry there. And this is giving me good inspiration for creating new research chemicals. Currently working on aryltrifluoroborates and aryltricyanoborates. They have potential as a catalizer for some cycloadditions.

[@LIVEMETRIX187]

any luck?

[@seankauder9721]

Undergrad ChemE. This was well suited to my knowledge level, I was familiar with 90% of the old-school synthesis

[@darkdevil905]

I have a degree in mathematical physics and all this organic chemistry stuff looks mental

[@moneymaker2109]

need u bro

[@NabilBreda]

I have a phd in chemistry but mathematics looks mental to me hahaha

[@Psilocybiant]

@@NabilBreda do your duty 😉

[@stochastic24]

Great video, I really appreciate the extensive description with timestamps and further information.

[@grantkoppelberger102]

I loved this video! I'm an undergraduate, but could easily follow until toward the end of the third part, where I just took your word for it. I enjoyed the quick history before jumping into the chemistry! I know it may be boring to many people, but I would love to see a video going through the full mechanism for different synthesis.

[@kaezaklimber3391]

4:25 "Back in those days, structural analysis was a master's craft" Very good content video. Make more videos please. Maybe also on old structural elucidation techniques... so cool

[@chelseadekle3532]

I'm not a chemistry major, yet I seem to know what I've learned from this experience in viewing your video explanation. Thanks for the very thorough review of lysergic acid synthesization and the basic history of its origins.

[@omarvela3154]

i have a mere bachelors in chemistry but used to study this synthesis in my college days very nice presentation and very well suited to my knowledge level. I work in an environmental lab and the chemistry is no where near as complicated or fascinating

[@whatcher8151]

your studies professional or pleasure, both? i had my day of perceptions. Can only look back a the puzzling adventure of a candid mind looking for the combination to reveal the answer to the next gate.

[@fergonsil1]

Good initiative! The history part was a really nice touch. I think that very often it gets neglected when studying a subject in chemistry and yet very interesting and helps in understanding how the knowledge was created. Answering your question, I think you should focus on easier approaches, for example not omitting some reaction mechanisms, that way you would captivate more public and would be easier to understand, just my personal opinion... I have a question also: is this a monthly series or will you be posting less or more frequently?

[@totalsynthesis]

Thanks Miguel! I'll try to make a new video every week!

[@smxnke]

I wish I learned organic chem like this. I really wish I had a teacher like you.

[@totalsynthesis]

Thank you - new video coming, stay tuned

[@smxnke]

I'm hooked

[@whatcher8151]

@@totalsynthesis and a red light. Then a broom to stick between my legs and jump over camp fires, ouch.

[@ethangormong7506]

My PhD advisor was a student of RBW! Such a brilliant mind

[@isura.m]

Man I wish I could understand, possess resources so that I can make my own acid

[@arrekesu6384]

Same bro maybe someday xdddd

[@covodex516]

Nothing prevents you from simply learning it yourself. Chemistry is a lot to take in at once when you're at the beginning and it will keep getting more complex when you dive deeper into it; but the basic principles behind it are very simple. With some will and determination, you can definitely teach it yourself with just the internet as your tool.

[@jeremiahshaw9349]

@@covodex516 thanks bro that helps alot. You're a chemist yourself?? and also there's online schooling for free and for profit that we have options to

[@covodex516]

@@jeremiahshaw9349 kind of - Im in my last semester of becoming a chemical technician (not to be confused with chemical worker), which is equivalent to a bachelor in chemistry but focussed on the chemical industry, means of production etc. (It also offers astonishingly high wage opportunities...^^) It really is a lot of work, especially at the start - the thing with chemistry is that you often have to learn several new things simultaneously because you need to understand one thing to be able to understand the other and vise versa. But as I said, the principles behind basically everything are very simple, because electrons, atoms and molecules follow very basic laws of physics; and most chemistry is mainly predicting what electrons on certain atoms will do under certain circumstances. So no, chemistry surely isn't easy and it definitely is A LOT of work in terms of learning, but it's also doable and super interesting. keep going for it!

[@isaackalashnikov3681]

Bruh if you don't understan the synthesis of the precursor, what makes you think you'll be able to make the finished molecule?

As a grad student in natural product synthesis a channel like this is music to my ears. Very nice first video, might wanna speak up a bit and put the mic much farther away, should sound better. Keep it up.

[@JustinKoenigSilica]

Oh, I also have a book reccomendation: ORGANIC SYNTHESIS: THE DISCONNECTION APPROACH by Stuart Warren! great for learning retro-synthesis. by the way: what's the dot @ 9:45? is that supposed to be a radical? is it a stereocenter? lastly, the product at 12:00 on the right is exactly the same as the one before it???

[@totalsynthesis]

Thank you for your comment. To answer your first questions: 1) That reagent is called pyridinium tribromide. The dot signifies just "an association" and you can think of it as a pyridine-HBr-Br2 complex; it's basically a source of electrophilic bromine. 2) The final molecule on the right is similar to the middle one but not exactly the same. The middle one contains the dihydroindole moiety which still needs to be dehydrogenated to give the unsaturated indole system.

[@readingisbelieving5248]

Just subscribed! It's great to see more chemistry youtubers!

[@jimparsons6803]

For a while there steroids was where it was at, the mid 50s to mid 60s, for anti-inflammatory uses and later for birth control. And in the mid 80s to about 2000 novel steroids, because of how the then and there laws were written (as I understood it), there were a lot of midnight labs making those newer steroids. I wonder if that might have turned out differently if there had been more trained chemists in the US Congress? Just a thought.

[@jimpinkowski3394]

Please show more of mechanisms - that is the interesting stuff! Thanks for explaining why the mechanistic pathway was chosen.

[@tokyorain3984]

Can you explain why adding the amide is so simple?

[@elnini415]

My recommendation; keep the videos advanced, this will influence more viewers to ponder off and do more research of the terms, and hopefully become more informed. Ps: great content (:

[@elnini415]

@@smartjared7203 nice marketing I used to own a spore company and do the same thing because I couldn’t run ads to a high risk business lol

[@danielcezar4599]

Thank you very much. Your scientific work is clear and motivating ...from an undergrad!

[@TheChrisBeattie]

Really interesting video as a grad student in total synthesis who wants to do some wider reading in an enjoyable manner! History is always interesting to hear about. Clear explanation of why certain strategies were employed and the potential pitfalls in the synthesis is always great to listen to. Look forward to more!

[@BrickForSheep]

2nd year analytical chemistry student, I definitely should be able to follow & draw out these mechanisms as I've learned them within the last 8 months or so. My sign to go back and work on them a bit more lol

[@JustinKoenigSilica]

Thanks man, came from your PM from reddit. good shit!

[@slippyq5336]

I thoroughly enjoyed your video. Not too tough, it challenges me to investigate what I don’t understand. Looking forward to your next video!

[@ArtuursPaulausks]

At 11:00, how do you get stereo specific Cl group attached ?

[@venkatrajnarayanan2785]

great video! As usual the history part gives better perspective for the why and how the synthesis was done! Enjoyed the chemistry mechanistic nuances...

[@dpjellema]

Great video! It was really interesting to watch and I really liked how you clearly explained the synthesis. Sometimes the video needed a bit more pace but that could just be my preference. Really looking forward to more videos!

[@loganclementi8947]

Wouldn't dry acetonitrille work as a solvent though? (Methyl cyanide versus hydrogen cyanide because it is pretty much nontoxic in comparison)

[@davidkimsey4424]

11:05 how did hydride reduction and acidification generate only that one chloro isomer and not racemic?

[@idontknowwhatthisis1]

This is a brilliant project and I hope you have plenty more videos planned! I'd like to echo other's requests for more mechanistic detail. For me (an undergraduate), and I'm sure for many others, arrow pushing is the best way to really to get to the heart of the chemistry that's happening.

[@ignomoly]

i kept thinking how all those molecules seem to be cut from... a giant hive... thanks for sharing...

[@marcochimio]

Wonderful description. One question, though: Can you explain why the last mechanism required a hydride shift? Couldn't that same hydrogen be released as a proton, leaving it's bonding electrons to form a double bond, pushing the position of the other two double bonds, resulting in the quenching of the indole N's positive charge and the formation of a Zn-enolate? Then that enolate could rearrange to the ketone? I assume that I'm missing something obvious, but what? Thanks (I'm not an organic chemist, but I have some understanding of all of the steps you showed.)

[@livingintheukandting]

Contrasting the classic and modern approaches was a good approach. This level of detail is just about perfect for undergrads, but as other people are saying more sterochem would be good - that's the hardest part!

[@totalsynthesis]

More advanced videos will be out in due time!

[@TheChrisBeattie]

Have to agree with ralph that I love the contrast of the classical approach with a series of simple robust steps, contrasted with a modern approach where the emphasis is on coupling reactions and rapid assembly of acyclic substrates.

[@joncrabb5926]

Man, I'm only in first year of a level chemistry so I don't understand this but I so want to this was a great video

[@totalsynthesis]

Nice, keep at it! Btw I'm working on another similar video so stay tuned

[@matthewabbott588]

yep I saw the indole to indoline. prob with any acid synth I thought and why woodward used the indoline and then oxidized too indole after making the back bone of the molecule first. lovely descriptions thankyou.

[@MrKrtek00]

Nice video! Generally, I phase out when reading papers (not an organic chemist), so it is very helpful to have such a discussion on strategies.

[@hellfirelordofevil]

This is very good overview of the subject! This sort of analysis of the synthesis is highly educational on how one aught to approach the retro-synthesis of complicated organic molecule.

[@vanessaaitkensilva4279]

I just needed some fun synthesis content and this was just perfect for me, thank u!!!!

[@Swagtildawn]

Absolutely love seeing stuff like this in regards to LSD and recreational drug use and not just lazy, biased stoner shit. Great video!

[@grinreaperoftrolls7528]

So I did really well in organic chemistry, and it’s my favorite class I’ve ever taken. The lilly-woodward synthesis was pretty simple. It is, however, absolutely terrifying 😂

[@blib3786]

Why is it terrifying?

[@shayneoneill1506]

Some people just click with it. A good friend of mine was a terrible student, and took nearly 6 years to finish his chemistry degree (partly because we spent so much time in the student union bar lol) but was an absolute genius with org chem from the outset. Meanwhile I know people who are brilliant physicists who can do navier stokes equasions in their sleep but had to take org chem twice due to flunking it first time. As a coder, we have our own equivelent, academic database theory. Some people like just intuitively get the relational calculus from day 1, some never get it and struggle with database theory all their lives. Somewhat Scandalously, one of the guys who wrote one of the more common SQL database textbooks admitted to me he still doesnt understand relational joins. Frankly his book should be withdrawn from circulation, but who am I to say, I'm just a lowly guy who has to clean up the mess left by the people misled by this idiots book.

[@christobalgonzalez3529]

Thanks for showing me how to make it. I was missing one small piece of info that was the HyP- 21∆° ¶π /33°×¥ Now it all makes sense

[@KnightsWithoutATable]

I was sent here by the algorithm, I swear officer.

[@HamzaAli-gg1jq]

Awesome content - keep it up!

[@zakirzak1494]

As a beginner and a novice to chemistry, I found it hard to digest .. I may need to watch it few more times to get an idea about it. Anyway your sincere work is appreciated... keep posting. Thanks

[@fmdj]

It's interesting. I understood approximately nothing but I like having a glimpse into how real chemists work. I'm just a beginner and a hobbyist, so it was totally my expectation that I would not understand much, but I still find this type of content quite inspiring. Then I'll probably head over to Scrap Science or some channel like that where a guy will make some acid (no pun intended) via the electrolysis of some salt - it'll be closer to my level of knowledge and skills :)

[@totalsynthesis]

😂😂 btw Ive just started to work on a video on the synthesis of cocaine (lol) - will probably only upload next month but you might find that interesting as well

[@fmdj]

@@totalsynthesis ahah awsome, I've always heard the synthesis of coke was so complicated that it made it totally not worth it economically, curious to see what this synthesis looks like.

[@maiawygle8835]

Would the lack of conjugation give way to higher intra substituion? I would be interested in a discussion of regioselectivity...

[@jacktennant6749]

This was really good! I liked this level of detail, but showing some electron-pushing mechs for each step would really help me see what’s going on!

[@gaatjeniksaan336]

isn't it possible to split ergotamine in the hydrogen bond, and then add a methyl group on the middle Nitrogen, and 2 ethyl groups on the Nitrogen group where the ergotamine got split in half?

[@Pootycat8359]

A very good book, by Hofmann, is, "LSD: My Problem Child." Hofmann didn't advocate the unrestricted availability of the drug, but felt responsible adults should have access to it, for personal use.

[@borat1]

Man I’m a high school chemistry student but I suck at it. This makes me want to learn so I can do some fun stuff like this.

[@MrTVx99]

Nice video man. As someone who struggles with organic chemistry, the explanations help out

[@erosionhead420]

It’s a fascinating history. God Bless Stanley Owsley. There’s a really great presentation he did before he died. It’s on the KZbin. Evidently,, he figured out the best method. I’m getting old and therefore,, only trip about one time a year now. 😊

[@lambdasun4520]

9:45 they didn't use a base because it would eliminate removing the hydrogen in the alpha position respect to the ketone thus creating a double bond, correct?

[@tcsynth]

An enolate would form, at which point Br2 would be attacked, brominating the alpha position and releasing Br-. The issue is that this can happen multiple times and the dibrominated product would result.

[@richardminton1786]

I found the history interesting. What chemist in this day says to themselves, "I will try it first!" ? Most of this is over my head but it does explain somewhat why some LSD is better than other LSD.

[@jrmooney2174]

i've always been curious as to whether or not those 3 other stereoisomers in the racemic mixture of LSD are *actually* non psychoactive or play any role in its effect

[@GroovyPancake]

Liking the video. Subscribed and looking forward to see how this channel grows

[@apppples]

Dude, I have a new channel to subscribe to! Hell yeah. Please more modern chemistry and mentions of stereochemistry. I just finished my advanced ochem courses on modern techniques and love seeing uses of the stuff I learned!

[@totalsynthesis]

Awesome, very happy to hear that!

[@DrBeah]

I always associate Eschenmoser with B12, but yes Hoffman was there too. more bios/articles would be great.

[@Bippah]

When I got your PM on reddit I really didn´t know what to expect... But this is amazing ! Keep up the great work! Also as an undergraduate student I´d love to see more of simpler synthesis; I really enjoyed the history parts aswell !

[@Lelvina]

As a Biology undergrad with almost 0 chemistry knowledge I did not understand anything, yet still watched the full video and enjoyed it? Maybe I`ll learn chemistry like babies learn language: all input ! lol

[@ScheveSneeuwSchuifSchep]

Same for me (Biology and medical lab research undergrad), I really want to understand this but I don't know where to start

[@roedurham3499]

Thank you fir yhis video this was an absolutely really great balanced video between science and history. It was so detailed with the science and just informative enough with the history that this made me super excited to rewatch and learn more about chemistry i really want to fluidly understand your chemical processes so i can smoothly follow along. But whT i did understand it was just way better than a lot of videos. Thank you very much

[@totalsynthesis]

Thanks for the kind words! I'm very happy to hear this.

[@حمزه-ش8ع]

This is an A class KZbin content

[@piperna5786]

Wow! What a channel!

[@shaunrempel9842]

I really enjoyed this. well put together. Good job. I would be interested in more videos like this

[@arturwojciechowicz3124]

Very good initiative.If J can suggest, two types videos(easier and advanced one) would be great on your channel.

[@arturwojciechowicz3124]

J'm waiting with excitement for new video, all in metaloorganic structures, at last it reached into me, thanks.

[@espanadorada7962]

Great video! Got a little lost near the end lol but I loved it all. The only thing I would change is maybe spend just a little time on some of the less obvious mechanisms for the “easy” part. I know it would help out a lot of people just learning those reactions connect their learning to this video and maybe give a little refresher to those of us who haven’t done ochem in a bit (hehe).

[@jonathansmith4634]

That was a great video. Thank you. I'm fairly new to Chemistry, so there is a lot that I have to learn.

[@mixla3493]

Can bromocriptine be converted to lsd? And how expensive/complicated it would be?

[@mixla3493]

@Danica Patrick ko Danice?

[@augustus4682]

Hell yeah man make a video on Woodward .. we'll love to see the great rare content

[@gmcenroe]

Woodward is one of my favorite organic chemists. That liquid HCN reaction condition looks pretty dangerous. Also if you read this old paper (as I did in the 1970s) you will notice that they did not have modern nmr spectrometers to characterize their products in the 1950s. Impressive but not a very practical route. I'm sure they ran into many roadblocks and problems to arrive at this route. I am now a recently retired medicinal chemist after many years in pharma research.

[@C134B]

I really enjoy watching woodwars master class on B12 synthesis, just... wow, like watching a physics class from feynman.

[@OsmioIridio-og8cn]

Great video.. thanks for sharing

[@cyberhops]

You're lecturing style is amazing. Love to listen

[@totalsynthesis]

Thanks!!

[@saysHotdogs]

your voice is like butter I feel like I've heard it narrating Legend of Zelda lore videos

[@chadkline4268]

I would've started with LSA extracts since that is the most practical source. Also, Dr. Randy Mills of Brilliant Light Power has developed a computer program that knows chemistry and can potentially compute routes of synthesis. It would be interesting to see a real chemist with an understanding of this program to see what novel routes of synthesis can be developed. Imagine if you could just have a program crunch away at all possible routes of synthesis 🙂 we're not quite there, but almost. Search for Millsian if interested.