title: The synthesis of (R)-(+)-lipoic acid using a monooxygenase-catalysed biotransformation as the key step.
abstract: 2-(2-Acetoxyethyl)cyclohexanone (4) was converted into the lactone (-)-(5) regio- and enantioselectively using 2-oxo-delta 3-4,5,5-trimethylcyclopentenyl acetyl-CoA monooxygenase, an NADPH-dependent Baeyer-Villiger monooxygenase from camphor grown Pseudomonas putida NCIMB 10007. The lactone (-)-(5) was converted into (R)-(+)-lipoic acid in six steps. In contrast cyclopentanone monooxygenase, an NADPH-dependent Baeyer-Villiger monooxygenase from cyclopentanol-grown Pseudomonas sp. NCIMB 9872 selectively oxidized the (S)-enantiomer of the ketone (4) giving better access to optically enriched, naturally occurring lipoic acid.
authors.affiliation: Chiroscience Ltd., Cambridge, U.K.
authors.forename: B
authors.initials: B
authors.lastname: Adger
authors.forename: M T
authors.initials: MT
authors.lastname: Bes
authors.forename: G
authors.initials: G
authors.lastname: Grogan
authors.forename: R
authors.initials: R
authors.lastname: McCague
authors.forename: S
authors.initials: S
authors.lastname: Pedragosa-Moreau
authors.forename: S M
authors.initials: SM
authors.lastname: Roberts
authors.forename: R
authors.initials: R
authors.lastname: Villa
authors.forename: P W
authors.initials: PW
authors.lastname: Wan
authors.forename: A J
authors.initials: AJ
authors.lastname: Willetts
mesh_terms: D001711:Biotransformation; D002384:Catalysis; D009682:Magnetic Resonance Spectroscopy; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D016958:Pseudomonas putida / Q000378:metabolism; D013237:Stereoisomerism; D008063:Thioctic Acid / Q000096:biosynthesis*
chemical_list: D008063:Thioctic Acid; C105909:2-oxo-delta(3)-4,5,5--trimethylcyclopentenyl acetyl-CoA monooxygenase; D009247:NADH, NADPH Oxidoreductases