An Efficient Chemoenzymatic Approach to (S)-γ-Fluoroleucine Ethyl Ester

• Published in: Journal of organic chemistry Vol. 70; no. 6; pp. 2372 - 2375
• Main Authors: Limanto, John, Shafiee, Ali, Devine, Paul N., Upadhyay, Veena, Desmond, Richard A., Foster, Bruce R., Gauthier, Donald R., Reamer, Robert A., Volante, R. P.
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 18.03.2005; Amer Chemical Soc
• Subjects: Aliphatic compounds; Catalysis; Chemistry; Chemistry, Organic; Exact sciences and technology; Glycosphingolipids - chemical synthesis; Lipase - chemistry; Molecular Conformation; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; IMIDATE SALTS; ASYMMETRIC-SYNTHESIS; ENANTIOSELECTIVE SYNTHESIS; N-METHYLACETIMIDATE; ALKYLATION; PHASE-TRANSFER CATALYSIS; ALPHA-AMINO-ACIDS; DIASTEREOSELECTIVE SYN-EPOXIDATION; STEREOSELECTIVE-SYNTHESIS; DYNAMIC KINETIC RESOLUTION; Catalytic reaction; Ethanol; Enzyme; Triacylglycerol lipase; Esterases; Leucine; Ring cleavage; Carboxylic ester hydrolases; Ester; Enzymatic method; Asymmetric synthesis; Aminoacid; Hydrolases; Carboxamide; Enantiomeric excess; Fluorine Organic compounds
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo047918j

An asymmetric synthesis of (S)-γ-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.