The synthesis of (R)-(+)-lipoic acid using a monooxygenase-catalysed biotransformation as the key step

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. (C) 1997, Elsevier Science Ltd.