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