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

• Published in: Bioorganic & medicinal chemistry Vol. 5; no. 2; pp. 253 - 261
• Main Authors: Adger, Brian, Bes, M.Teresa, Grogan, Gideon, McCague, Raymond, Pedragosa-Moreau, Sandrine, Roberts, Stanley M., Villa, Raffaella, Wan, Peter W.H., Willets, Andrew J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-1997
• Subjects: Biotransformation; Catalysis; Magnetic Resonance Spectroscopy; NADH, NADPH Oxidoreductases - metabolism; Pseudomonas putida - metabolism; Stereoisomerism; Thioctic Acid - biosynthesis
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(96)00234-9

2-(2-Acetoxyethyl)cyclohexanone (
4) was converted into the lactone (−)-(
5) regio- and enantioselectively using 2-oxo-Δ
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.
A monooxygenase enzyme is employed in the kinetic resolution of the ketone (±)-(
4) to provide optically active lactone (−)-(
5), an intermediate to naturally occurring lipoic acid.