AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER

A Simple Organocatalytic Enantioselective Synthesis of Pregabalin

 Uncategorized  Comments Off on A Simple Organocatalytic Enantioselective Synthesis of Pregabalin
Jun 022015
 

Bassas, O.; Huuskonen, J.; Rissanen, K.; Koskinen, A.M.P. ’A Simple Organocatalytic Enantioselective Synthesis of Pregabalin.’ Eur. J. Org. Chem. 2009, 1340-1351.

 

 

 

This paper describes a new procedure for the enantioselective synthesis of the important anticonvulsant drug Pregabalin, which shows biological properties as the (S) enantiomer only. The key step of the synthetic sequence is the Michael addition reaction of Meldrum’s acid to a nitroalkene mediated by a quinidine derived thiourea. A variety of novel catalysts bearing different groups at the thiourea moiety were synthesized and tested. The most successful catalyst that incorporates a trityl substituent provided up to 75 % ee of (S)-4. The conjugate addition reaction was carried out on a multigram scale with low loadings of catalyst (10 mol-%). Moreover, the catalyst can be recycled showing the same capability in chemical yield and asymmetric induction. Then, hydrogenation of nitroalkane 4 followed by decarboxylation of diacid 5 provides Pregabalin hydrochloride in 59 % overall yield. Enantioenrichment by crystallization of the free amino acid 1 improves the (S)/(R) enantiomeric ratio to 9:1.

Author Information

  1. 1Department of Chemistry, Helsinki University of Technology, P. O. Box 6100, 02015 TKK, Espoo, Finland, Fax: +358-94512538
  2. 2NanoScience Center, Department of Chemistry, University of Jyväskylä, P. O. Box 35, 40014 Jyväskylä, Finland
  1. X-ray crystallography.

Email: Ari M. P. Koskinen (ari.koskinen@hut.fi)

http://onlinelibrary.wiley.com/doi/10.1002/ejoc.200801220/abstract

 

 

Jyväskylä, Finland

TAKE A TOUR

 

 

Jyväskylä, Finland

 

  1. Jyväskylä – Wikipedia, the free encyclopedia

    en.wikipedia.org/wiki/Jyväskylä

    Jyväskylä (Finnish pronunciation: [ˈjyvæsˌkylæ]) is a city and municipality in CentralFinland in the western part of the Finnish Lakeland. It is the largest city in  …

    History – ‎Etymology – ‎Government – ‎Geography

 

 

 

 

 

 

 

 

 

///////////

Share
Follow

Get every new post on this blog delivered to your Inbox.

Join other followers: