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.
Adger
B
B
Chiroscience Ltd., Cambridge, U.K.
Bes
M T
MT
Grogan
G
G
McCague
R
R
Pedragosa-Moreau
S
S
Roberts
S M
SM
Villa
R
R
Wan
P W
PW
Willetts
A J
AJ
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*
D008063:Thioctic Acid; C105909:2-oxo-delta(3)-4,5,5--trimethylcyclopentenyl acetyl-CoA monooxygenase; D009247:NADH, NADPH Oxidoreductases