Synthesis of natural product precursors by Baeyer-Villiger oxidation with cyclohexanone monooxygenase from Acinetobacter

The Baeyer-Villiger oxidation of the 2-substituted ketones 1 and 3 with the coupled system cyclohexanone monooxygenase from Acinetobacter NCIMB 9871 / formate dehydrogenase from Pseudomonas sp. 101 provides the lactones (R)-2 and (R)-4 with high enantiomeric excess which are precursors in the synthesis of lipoic acid. The symmetrically trisubstituted ketone 5 was oxidised to the lactones 6a and 6b in a ratio of approx. 3:1. The absolute configuration of 6a and 6b was determined by hydrolysis of the racemic lactone with PLE yielding the hydroxycarboxylic acid (-)-7 with known absolute configuration.</p