Sciencemadness Discussion Board

Related Topics: Synthesis and Isolation of Antibiotics and Drugs?

DarkswordDX - 9-4-2008 at 19:34

Greetings. New member and long time lurker here.

I'm sorry to make the classical newbie move of barging in and asking for things without first contributing something meaningful, but my personal forte is that of a student of the Physical sciences, so chemistry is less of my field than mathematics or physics.

I'd like to request the help of the knowledgeable souls here in a most worthwhile endeavour. I'm in the process of writing a historical pharmaceutical manual for my own reference. It's primarily going to be an informational piece, with a high level of practicality in certain situations. The idea being to compile instructions for the preparation of certain medical drugs in an environment that has no modern amenities. A "Where there is no Doctor" situation, for anyone familiar with that book.

To start the compilation, I went back to the sources: Pharmacology from turn-of-the-century through the WW2 era. My difficulty comes from a lack of chemistry background (never went past Chem 110) in understanding how to isolate or synthesize the various elements of these early medical treatments. Compound that with an almost complete lack of available texts which describe the early productions in reproducible detail. And in particular where to obtain the necessary components in as primitive a form as possible. Some of them are derived from biological sources, and I'm hoping those more gifted in biology than I might have an understanding of how to harvest them. Also, I know that several members of the forum here have access to impressive libraries of antiquated lab manuals and texts.

Examples that I'm looking for in particular are:

Antibacterial sulfonamides
Preparation of Penicillin in small quantity by the earliest methods
Chloramphenicol
Mercurochrome
Streptomycin
Tetracycline
Fusidic acid
Clavulanic acid
Extraction and concentration of acetylsalicylic acid

Can anyone contribute? Even the details of the original experiments would be most useful. I'll be lurking the boards, and will return the favor whenever I see a question I might be able to answer.

Sauron - 10-4-2008 at 03:09

My advice is: get yourself a Merck Index. You can download this free from References, once you qualify to get the PW. (You are halfway there.)

Merck will point you at the primary or secondary literature.

Also obtain the US and British Pharmacopeias. Likewise from References.

Some of the compounds you asked about are simple and easy. Like, extract acetylsalicyclic acid from what? You make salicylic acid (2-hydroxybenzoic acid) and then you acetylate the phenolic -OH. It is entirely a synthetic. (It of course is Aspirin.)

Chloramphenicol, similarly. A simple benzene derivative.

There are very many sulphonamides, and the general structure is that they are amides of various aromatic sulphonic acids. You could write a book on the sulfa drugs alone.

Penicillin. tetracycline, streptomycin, these are very complex compounds and very far removed from the simple items above.

Mercurochrome? An obsolete topical antiseptic. What can you do with mercurochrome that you can't do better with Betadine?

Anyway, as I said, get Merck, and get the USP and BP. and they will keep you busy for a long while.

not_important - 10-4-2008 at 04:32

You will also find that there are several older pharmacopoeias on line, available for free download, and some compilations of American Druggist as well. These are practical books from a century to a century and a half years ago, giving about as detailed methods are you are likely to find. The the Internet Archive and then Google Books.

"Extraction and concentration of acetylsalicylic acid" ?? You make it from salicylic acid, which is made from sodium phenolate and CO2.

sparkgap - 10-4-2008 at 07:39

"There are very many sulphonamides, and the general structure is that they are amides of various aromatic sulphonic acids. You could write a book on the sulfa drugs alone. "

Somebody already has written an entire book very recently; it's part Domagk biography and part sulfonamide history. "The Demon Under the Microscope" is the title.

The antibiotics most certainly are not prepared; you get it from the appropriate species of fungus or bacterium in the soil. Seeing that your aim is "the idea being to compile instructions for the preparation of certain medical drugs in an environment that has no modern amenities.", you'd have to be pretty sure that you are in fact isolating the appropriate microbe and not some pathogen or toxin producer. Pretty difficult with the conditions you set. Plus the fact that these producers are not too widespread.

You'd have better luck getting iodine from seaweed than making Mercurochrome. ;)

sparky (~_~)

[Edited on 10-4-2008 by sparkgap]

Bolt - 16-4-2008 at 18:06

The six volume Organic Chemistry of Drug Synthesis from Wiley is a good starting point. At one time I checked out the first volume from my university library. It was an informative read, with lots of syntheses that I could perform in my bathtub if I wanted to. (You'd be amazed at the number of useful drugs that you can make from cocaine.) Unfortunately, most of the 'simple' drugs have a lot of bad side effects... even if you get very, very pure products.

PainKilla - 16-4-2008 at 22:35

This is just a taste of what may be to come... Most of them are worse, since you need to culture bacteria and extract the active product, and depending on what it is, further modify it. I am not familiar with the processes involved, but it wouldn't surprise me one bit that some of the bacteria in question are also pathogenic. All in all, not something I'd want to do at home. There are some simpler antibiotics you could make (sulfonamides) at home, the rest are really rather difficult however, as even isolating a pure culture is quite time consuming.

Such a book would be neat, but probably impractical to all but the most well equipped labs, IMHO anyway.

The procedure is from Kleeman and Engels - Pharmaceutical Substances (4th Edition).

Chloroamphenicol.JPG - 192kB

sparkgap - 17-4-2008 at 04:22

As a matter of fact, chloramphenicol is one of the few drugs where synthesis has shown itself to be much more economically feasible than extraction from the natural source. ;)

sparky (~_~)

ShadowWarrior4444 - 8-5-2008 at 12:14

Quote:
Originally posted by not_important
You will also find that there are several older pharmacopoeias on line, available for free download, and some compilations of American Druggist as well. These are practical books from a century to a century and a half years ago, giving about as detailed methods are you are likely to find. The the Internet Archive and then Google Books.

"Extraction and concentration of acetylsalicylic acid" ?? You make it from salicylic acid, which is made from sodium phenolate and CO2.


The original genesis of acetylsalicyclic acid was from analysis of salicylate-rich Willow bark, which has been used since antiquity for its aspirin-like properties. More specifically, salicyclic acid and salicin are extracted from Salix alba, the white willow from which it derives the name 'salicylic.'

As for extraction process-- the inner bark of the Salix alba has been made into aqueous infusions for the relief of pain, the active ingredient involved is Salicin. The Willow bark may also be macerated in alcohol to provide a tincture. Salicylic acid itself can also be extracted from Meadowsweet (Filipendula ulmaria,) though taken as-is, it has been known to cause gastrointestinal difficulties. If you have a sodium base, you may be able to convert the extracted Salicylic acid to Sodium Salicylate then react that with acetyl chloride to replicate the orginal synth.

Peruvian Bark (several species of the genus Cinchona, of the order Rubiaceae,) also contains quinine, should you have occasion to combat malaria infections. A mixed water infusion of Peruvian Bark and Salix alba also gained popularity against malaria, as the Salicin alleviated the symptoms, while the quinine cured the disease.

It should be noted that you do not necessarily need acetylsalicylic acid for pain relief, the acetyl group does make it easier on the stomach though.

Penicillium chrysogenum is the mold that makes penicilin, adding a treatise on plant/mold/fungus identification to your book would be invaluable to survivalists and those without modern amenities as it would provide guidelines for finding food, making medicinal constructs, and synthesizing poisons for hunting.

Remember, you don’t necessarily need to have a *pure* product for it to be effective, it just needs to be free of anything reasonably deadly.

Another small note: The above did not take any great feat of research nor did it require that I break out my enjoyably large reference books--a slight bit of Googling and a wee bit of historical reading will give you a firm base upon which to start your research, after that you may wish to look up specific references and perhaps make your own improvements if you feel comfortable with it.

[Edited on 5-8-2008 by ShadowWarrior4444]