title: A chemo-enzymatic route to synthesize (S)-γ-valerolactone from levulinic acid.
abstract: Levulinic acid is a feasible platform chemical derived from acid-catalyzed hydrolysis of lignocellulose. The conversion of this substrate to (S)-γ-valerolactone ((S)-GVL) was investigated in a chemo-enzymatic reaction sequence that benefits from mild reaction conditions and excellent enantiomeric excess of the desired (S)-GVL. For that purpose, levulinic acid was chemically esterified over the ion exchange resin Amberlyst 15 to yield ethyl levulinate (LaOEt). The keto ester was successfully reduced by (S)-specific carbonyl reductase from Candida parapsilosis (CPCR2) in a substrate-coupled cofactor regeneration system utilizing isopropanol as cosubstrate. In classical batch experiments, a maximum conversion of 95 % was achieved using a 20-fold excess of isopropanol. Continuous reduction of LaOEt was carried out for 24 h, and a productivity of more than 5 mg (S)-ethyl-4-hydroxypentanoate (4HPOEt) per μg CPCR2 was achieved. Afterwards (S)-4HPOEt (>99%ee) was substituted to lipase-catalyzed lactonization using immobilized lipase B from Candida antarctica to yield (S)-GVL in 90 % overall yield and >99%ee.
authors.affiliation: Institute of Technical Biocatalysis, Hamburg University of Technology, Denickestraße 15, 21073 Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Götz
authors.forename: Andreas
authors.initials: A
authors.lastname: Liese
authors.forename: Marion
authors.initials: M
authors.lastname: Ansorge-Schumacher
authors.forename: Lutz
authors.initials: L
authors.lastname: Hilterhaus
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D002175:Candida / Q000201:enzymology; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism*; D007982:Levulinic Acids / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D007783:Lactones; D007982:Levulinic Acids; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C037556:gamma-valerolactone