title: Chemoenzymatic synthesis of vitamin B5-intermediate (R)-pantolactone via combined asymmetric organo- and biocatalysis.
abstract: The combination of an asymmetric organocatalytic aldol reaction with a subsequent biotransformation toward a "one-pot-like" process for the synthesis of (R)-pantolactone, which to date is industrially produced by a resolution process, is demonstrated. This process consists of an initial aldol reaction catalyzed by readily available l-histidine followed by biotransformation of the aldol adduct by an alcohol dehydrogenase without the need for intermediate isolation. Employing the industrially attractive starting material isobutanal, a chemoenzymatic three-step process without intermediate purification is established allowing the synthesis of (R)-pantolactone in an overall yield of 55% (three steps) and high enantiomeric excess of 95%.
authors.affiliation: †Faculty of Chemistry, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Heidlindemann
authors.affiliation: ‡Department of Chemistry, University of Cologne, Greinstrasse 4, 50939 Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hammel
authors.affiliation: †Faculty of Chemistry, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.|§Institute of Chemistry, Humboldt University, Brook-Taylor-Straße 2, 12489 Berlin, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Scheffler
authors.affiliation: §Institute of Chemistry, Humboldt University, Brook-Taylor-Straße 2, 12489 Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Mahrwald
authors.affiliation: ∥Institute of Molecular Enzyme Technology, Heinrich Heine University of Düsseldorf, Research Centre Jülich, Stetternicher Forst, 52426 Jülich, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hummel
authors.affiliation: ‡Department of Chemistry, University of Cologne, Greinstrasse 4, 50939 Cologne, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Berkessel
authors.affiliation: †Faculty of Chemistry, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Gröger
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000426:Alcohol Dehydrogenase / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D055162:Biocatalysis; D001711:Biotransformation; D002384:Catalysis; D006639:Histidine / Q000737:chemistry*; D015394:Molecular Structure; D010205:Pantothenic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D010205:Pantothenic Acid; D006639:Histidine; C005412:pantolactone; C116609:3-hydroxybutanal; D000426:Alcohol Dehydrogenase; D015107:4-Butyrolactone