(+)-Prostaglandin PGF2a
Update 16-09-12: just found out that this has also been written about over at the greenchemblog. If you fancy an alternative take with more detail and less history, look over there!
Stereocontrolled organocatalytic synthesis of prostaglandin PGF2α in seven steps
Aggarwal et al., Nature, 2012 [PDF] [GROUP] [SI]
DOI: 10.1038/nature11411
I’ve heard it said a few times that if you can’t be the first to synthesise a natural product, then you should try and be the last; that is, you should aim to come up with the most elegant and efficient route you can now that the pressure’s off and there’s less of a rush. I think that some really popular molecules are still waiting for a ‘last’ synthesis (e.g. taxol), as even the best routes devised to date still seem ‘too long’ and are larded with too many oxidation level adjustments and protecting group juggling steps. Obviously synthetic organic chemistry – like any science – is constantly improving so the aim is to devise the best solution possible at the time, and to learn something along the way. A good synthesis is timeless.[1]
BRSM Reviews: Taxol In 10 Minutes
If you're reading this then I reckon you've probably heard of taxol, as it's one of the most talked about synthetic targets of all time. It's a molecule with a fascinating history, from its isolation and structural assignment in 1971, to discovery of its potent activity and interesting mode of action, and the ensuing scrabble to solve the supply problems plaguing its development as a drug.[1] Its rise to success as a billion dollar pharmaceutical was stellar, and is one of my favourite examples of how useful and important synthetic organic chemistry is. Although it's been 5 years since the most recently reported synthesis of taxol, last week's Baran synthesis of taxadiene (following his cyclase-oxidase mimic plan for elaboration of this hydrocarbon into taxol) seems to have again gotten chemists talking excitedly about this target. After overhearing things like 'didn't Nicolaou make it first?', 'there've only been x syntheses so far' (where x is 0-6) and other such misinformation in our office I've decided to take action. Yes, there are already numerous reviews, book chapters and even entire books on this subject, but it seems that a lot of people don't have the time or inclination to read them. So, here's a brief summary of the 7 syntheses published so far, in the order they were completed. Hopefully this'll help put recent developments in perspective.