Enantioselective whole cell and isolated enzyme catalysed Baever-Villiger oxidation of bicyclo[3.2.0]hept-2-en-6-one

Abstract

Bicyclo[3.2.0]hept-2-en-6-one (Fig. 1, 1) was subjected to Baeyer-Villiger type oxidation using whole cells of Acinetobacter NCIMB 9871, Acinetobacter junii, Pseudomonas putida, Rhodococcus coprophilus, Rhodococcus fascians and cyclohexanone monooxygenase which had been purified 20-fold from Acinetobacter NCIMB 9871. In all cases, when the racemic ketone was oxidased, equal quantities of the regioisomeric lactones (−) 1( S),5( R) 2-oxabicyclo[3.3.0]oct-6-en-3-one (Fig.1, 3) and (−)-1 ( R), 5( S) 3-oxabicyclo[3.3.0]oct-6-en-2-one (Fig. 1, 4) were formed in high enantiomeric excess. The results were compared with peracid and alkaline peroxide mediated oxidations which showed no enantioselectivity towards the racemic ketone substrate and yielded only low amounts of 3-oxabicyclo[3.3.0]oct-6-en-2-one. Further investigation using purified cyclohexanone monooxygenase showed that the (+)-enantiomer was oxidised to 2-oxabicyclo[3.3.0]oct-6-en-3-one (Fig. 1, 3) whilst the (−)-enantiomer was oxidised to 3- oxabicyclo[3.3.0]oct-6-en-2-one (Fig. 1, 4). Both lactone products have potential applications as chirons for the synthesis of compounds containing cyclopentane and cyclohexane rings. The development of a chiral gas chromatography method allowed the rapid and accurate determination of the enantiomeric purity of bicyclic ketones and lactones.