B.R.S.M. To strive, to seek, to find and not to give a yield

5Nov/126

Mulvember 1: Introduction and Penifulvin A

Like many research groups, the one I’m in does weekly literature talks so people get a bit of practice with powerpoint and public speaking. Because excessive freedom can be a bit daunting, although people are free to choose the topic of their own talk it has to fit in with a particular theme, which, at the moment, is living Germanic chemists. In this vein, last month I wrote and gave a talk on the life and work of Johann Mulzer. Now, as I've been a bit busy lately, and the literature has been a bit lacking in interesting total syntheses, I've decided to rehash my talk as a series of blog posts. On the upside, this should mean more posts for you guys and less hassle for me (as I've already drawn everything in ChemDraw). Also, although I didn't know this when I wrote the talk, it seems that Mulzer is finally winding down and I think he deserves a bit of send-off. I, for one, have learnt a lot from reading his papers over the past few years.

From a recent Angewandte paper.

Unfortunately, most of the syntheses that I covered in my talk are already pretty well known, and many of them have also already been covered on Totally Synthetic at one time or other. Still, if you missed somehow missed reading about them there or prefer my more rambling style then read on!

Incidentally, if you’re wondering what the German text on the slide is all about, it’s taken from the group website and is usually rendered (non-literally) in English as ‘no battle plan survives contact with the enemy’, something all chemists who have worked in total synthesis know well![1]

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28Jul/114

Solve your deprotection problems… with TNT

A busy week in the lab trying to finish this damn natural product. More things at the weekend.

Update 30/07/11: Forgot to give a reference for the Hoffmann paper, which is Angew. Chem. Int. Ed., 1993, 32, 101-103. It's not a bad piece of work, and was for a time the shortest route, despite being entirely linear.

Johann Mulzer, one of my favourite chemists, wrote a review back in 1991 titled 'Erythromycin Synthesis—A Never-ending Story?'. It's well worth a read as these natural products have inspired an awesome body of work, and were an important benchmark in stereoselective natural product synthesis for many decades. Woodward, Stork, Corey, Danishefsky, Evans, Paterson, Reinhard Hoffmann, Mulzer, Carreira and most recently White have all worked on them, which is some recommendation.[1]

Anyway, I was reading Hoffmann's synthesis of (9S)-dihydroerythronolide A today when I encountered a most unusual set of conditions for deprotection. To set the problem in context, the (unstable) triply protected compound below had been obtained, and only three steps remained to the glorious completion of the target; selective cleavage of the cyclopentylidene acetal, macrolactonisation (assisted by the conformation limiting p-methoxybenzylidene acetals) and a final deprotection. The problem was that the cyclopentylidene acetal couldn't be removed without cleaving the other protecting groups, despite encouraging results obtained earlier in model studies. Not wanting to start again, a method to slow down hydrolysis of the p-methoxybenzylidene acetals was needed.

Filed under: Fun, Lab, Serious | 11,514 views | 4 comments Continue reading