Perhaps not unexpectedly, given last year's exciting breakthrough syntheses, more synthetic work on the weltwitindolinones appeared in the literature last week, so I think an update is in order. As a reminder, the first synthesis of a bridged bicyclic member of this family came in March last year when Rawal reported a neat racemic route to N-methylwelwitindolinone D isonitrile, emerging as the winner of a 15 year race between plenty of well known synthetic chemists. This was rapidly followed by Garg, who published an excellent synthesis of (-)-N-methylwelwitindolinone C isothiocyanate in August, which I covered here.
Well, two more back to back JACS papers, one each from Rawal and Garg have just appeared, and I'll summarise both here. Garg's describes improvements to the key step in his previously reported route to (-)-N-methylwelwitindolinone C isothiocyanate, along with the synthesis of (-)-N-methylwelwitindolinone C isonitrile and a couple of the so-called 'oxidised welwitindolinones'. Rawal's contains an asymmetric version of his previous racemic route, allowing access to (-)-N-methylwelwitindolinone C isothiocyanate/isonitrile, along with one of the 'oxidised welwitindolinones'. As Rawal’s has the most new chemistry of the two we'll look at that first.
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. 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.