An efficient chemoenzymatic approach to (S)-gamma-fluoroleucine ethyl ester.

John Limanto, Ali Shafiee, Paul N Devine, Veena Upadhyay, Richard A Desmond, Bruce R Foster, Donald R Gauthier, Robert A Reamer, R P Volante

Department of Process Research, Merck Research Laboratories, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. john_limanto@merck.com

The Journal of organic chemistry 2005 Mar 18

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reaction: see text] An asymmetric synthesis of (S)-gamma-fluoroleucine ethyl ester 1 is described. The key transformation involves a lipase-catalyzed dynamic ring-opening of 2-(3-butenyl)azlactone 7b with EtOH to give amide ester (S)-6b in 84% enantiomeric excess. Removal of the N-pentenoyl group with N,N'-dibromodimethylhydantoin in the presence of trifluoroacetic acid afforded the titled compound, which was isolated as its hydrogen sulfate salt in 75% yield and >97% ee.

Citation

John Limanto, Ali Shafiee, Paul N Devine, Veena Upadhyay, Richard A Desmond, Bruce R Foster, Donald R Gauthier, Robert A Reamer, R P Volante. An efficient chemoenzymatic approach to (S)-gamma-fluoroleucine ethyl ester. The Journal of organic chemistry. 2005 Mar 18;70(6):2372-5