Sciencemadness Discussion Board

Synthesis of vitamin B12

thesmug - 29-4-2014 at 14:00

This isn't a question on how to synthesize B12 but rather, has anyone ever tried to synthesize vitamin B12? While looking at its structure I suddenly thought this and it's stuck in my head. I've looked but I couldn't find any resources on this. It seems like it would be a ton of work for no reason as it is extractable from other things.

VitaminX - 29-4-2014 at 14:45

The term you seem to be searching for is "total synthesis" and yes, there have been various published for Vitamin B12.
The first one is from Woodward in the 60's:

http://www.synarchive.com/syn/71

Pretty crazy synthesis as you can see, here's the wiki article on the subject:

http://en.wikipedia.org/wiki/Vitamin_B12_total_synthesis

You are right that, with many natural products, total synthesis is not necessary though it has often helped clear up structural errors in suggested structures and it has a few industrial scale applications (Palcitaxel if I'm not mistaken) though mostly TS is done for moving forward and developing new methods in organic synthesis and, on the other hand, to prove that if you throw enough post-docs at a molecule you CAN synthesize everything.

[Edited on 29-4-2014 by VitaminX]

AvBaeyer - 29-4-2014 at 18:28

The total synthesis of B12 by Woodward and Eschenmoser is one of the greatest achievements of organic synthesis. Out of this work emerged the Woodward-Hoffman rules on the theoretical side and HPLC as a routine tool on the practical side. Also, careful reading of the many papers which emerged from this grand undertaking reveal the invention of new reactions as well as the imaginative use of existing reactions. B12 also inspired others to attempt its synthesis, in particular the isoxazole approach of the R V Stevens group. All this is classic organic chemistry at its finest - not a palladium coupling reaction in sight!!

I encourage you to track down and read the papers concerning this still stimulating but now classic work

AvB

thesmug - 1-5-2014 at 06:00

Would it be possible at all to do this in a home setting :D? Not that I intend to try but it seems that anyone with at least a moderate knowledge of organic chemistry should be able to follow the synth. posted above.

kavu - 1-5-2014 at 06:20

Quote: Originally posted by thesmug  
Would it be possible at all to do this in a home setting :D? Not that I intend to try but it seems that anyone with at least a moderate knowledge of organic chemistry should be able to follow the synth. posted above.


In theory, yes, you could replicate any published synthesis (try brevetoxin-b for example). Practically ... no. The amount of work and money needed is immense. Also some of the reactions are very tricky to get to proceed, not to mention the purifications. The Woodward era syntheses also rely on starting with kg scale of material which is not something I'd readily start doing at home. There's also the problem that these early total syntheses aren't very well documented and the synthetic descriptions can be very vague.

[Edited on 1-5-2014 by kavu]

AvBaeyer - 1-5-2014 at 17:12

The synthesis of B12 took the efforts of many, many post-docs and untold numbers of graduate students working at both Harvard and at ETH. The effort required well over 10 years to complete. I myself worked on the Stevens approach as a post-doc for two years just trying to perfect two reactions. Truly, track down the publications associated with the Woodward-Eschenmoser work and read them for pure pleasure. There's more organic chemistry in them than one could ever do in a lifetime. Also, check out the Stevens approach and study it just for its conceptual elegance.

AvB