Synthesis of Natural Product Precursors by Baeyer-Villiger Oxidation with Cyclohexanone Monooxygenase from Acinetobacter

Abstract

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.

Key words

oxidation - enzymes - kinetic resolution - hydrolysis - natural products

References

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  Present address: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.; E-mail: mailto:[e-mail]

• 1b

  New address: U. Kragl, University of Rostock, Department of Chemistry, Buchbinderstrasse 9, 18051 Rostock, Germany, Fax [phone], E-mail: [e-mail]

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  Details of the enzyme preparation will be reported in due course.

30

The reaction was published without any experimental details.

32

The lactone (R)-2 was described only in ref. 27 but without any physical data.