On the resolution of chiral substrates by a retro-claisenase enzyme: Biotransformations of heteroannular bicyclic beta-diketones by 6-oxocamphor hydrolase

Cheryl L. Hill, Lee Chiang Hung, Derek J. Smith, Chandra S. Verma, Gideon Grogan

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The enzyme 6-oxocamphor hydrolase (OCH) from Rhodococcus sp. NCIMB 9784 catalyses the cleavage of a carbon-carbon bond between two carbonyl groups in both mono- and bicyclic non-enolisable beta-diketone substrates. In this mode OCH has been shown to effect the desymmetrisation of both bridged symmetrical bicyclic [2.2.1] and [2.2.2] systems and a series of 1-alkylbicyclo[3.3.0]octane-2,8diones, yielding chiral substituted cyclopentanone and cyclohexanone products in high optical purity. In the present study, OCH has been challenged with a series of heteroannular substrates including 1-methylbicyclo[4.3.0]nonane-2,9-dione (7a-methylhexahydroindene-1,7-dione) in an effort to assess the competence of the enzyme for kinetic resolutions of asymmetric, racemic substrates. OCH was shown to catalyse the resolution of I-methylbicyclo[4.3.0]nonane-2,9-dione with an E value of 2.9. The effect of increasing the length of the alkyl chain in the 1-position, or enlarging one of the rings, was to increase the enantioselectivity of the enzyme to 5.7 and 3.1 for the substrates 1-allylbicyclo[4.3.0]nonane-2,9-dione (7a-allylhexahydroindene1,7-dione) and 1-methylbicyclo[5.3.0]decane-2,10-dione (8a-methyloctahydroazulene-1,8-dione), respectively. 1-Methylbicyclo[5.4.0]undecane-2,10-dione (9a-methyloctahydrobenzoeycloheptene-1,9-dione) was not a substrate for OCH. These experiments constitute the first description of the resolution behaviour of such a retro-Claisenase enzyme, and suggest a maximum steric limit for substrate recognition by OCH.

Original languageEnglish
Pages (from-to)1353-1360
Number of pages8
JournalAdvanced Synthesis and Catalysis
Issue number8-9
Publication statusPublished - Jun 2007


  • biotransformations
  • chemoenzymatic synthesis
  • beta-diketones
  • enzyme catalysis
  • enzymes lyases

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