An efficient chemoenzymatic approach to (S)-gamma-fluoroleucine ethyl ester.
[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.
Limanto
John
J
Department of Process Research, Merck Research Laboratories, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. john_limanto@merck.com
Shafiee
Ali
A
Devine
Paul N
PN
Upadhyay
Veena
V
Desmond
Richard A
RA
Foster
Bruce R
BR
Gauthier
Donald R
DR
Reamer
Robert A
RA
Volante
R P
RP
D002384:Catalysis; D006028:Glycosphingolipids / Q000138:chemical synthesis*; D008049:Lipase / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism
C500924:(2S,3S,4R)-1-O- (alpha-D-galactosyl)-2- tetracosanoylamino-1,3,4-nonanetriol; D006028:Glycosphingolipids; D008049:Lipase