What is the right configuration again ?

Happy St. Patrick’s Day.  (Sorry this is an old post)   Okay, happy belated.  I had intended to get this out yesterday.  I figured I would post a quick posting today.   This is quite a wild story when I read the article.  Did you come by it, by chance ?  Last week, I was talking about continuous flow and its application to artemisinin, a needed anti-malaria drug.  I was looking through my pile of papers to talk about and came across this paper, again about a anti-malaria drug.  The paper was called “Determining the Absolute Configuration of (+)-Mefloquine HCl, the Side-Effect-Reducing Enantiomer of the Antimalaria Drug Lariam”, by Uwe. M. Reinscheid et al, J. Am. Chem. Soc, J. Am. Chem. Soc.2012134 (6), pp 3080–3083 DOI: 10.1021/ja209050k.  I just thought this was an interesting read in this time and age.   Racemates are still sold, ones where each enantiomer have different, possibly detrimental activities ?  I thought that was stopped after the Thalidomide incident.  Apparently not.

 

 

mefloquine

I think it might be a problem selling an anti-malaria drug where one of the enantiomers causes psychosis, don’t you ?  This product had been sold for decades and according to Wikipedia ( a great and trusted resource, I guess this is dripping with a bit of sarcasm), Lariam was developed as a synthetic analog of quinine in the 70s.  http://en.wikipedia.org/wiki/Mefloquine.  Apparently, this drug is still made and available in generic form.

Despite the fact that this molecule has been revisited quite a few times in the past to determine its absolute configuration, the authors of this paper conclusively through the use of RDC (residual bipolar coupling) NMR, optical rotation dispersion (OCD) and circular dichroism data, determined the proper configurations for both enantiomers.  It is expected that this will lead to a promising treatment with fewer side effects.  I had to share this story.   It astounds me that such a simple molecule could have lasted this long without its correct absolute configuration being known.

 

 

 

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