Desymmetrisations of 1-alkylbicyclo[3.3.0]octane-2,8-diones by enzymatic retro-Claisen reaction yield optically enriched 2,3-substituted cyclopentanones

Cheryl L. Hill, Chandra S. Verma, Gideon Grogan

Research output: Contribution to journalArticlepeer-review

Abstract

A series of 1-alkylbicyclo[3.3.0]octane-2,8-diones was transformed by enzymatic retro-Claisen reaction using recombinant 6-oxocamphor hydrolase (OCH) overexpressed in Escherichia coli, to yield optically active 2,3-substituted cyclopentanones with enantiomeric excesses of up to > 95 %. Whilst the parent substrate, bicyclo[3.3.0]octane-2,8-dione 12, was transformed only very slowly, derivatives 13, 14, 15, 16 and 30 with alkyl chains of varying length in the 1-position were converted rapidly to optically active products with typically 82% de and up to > 95 % enantiomeric excess. The results confirm the apparent requirement of OCH for non-enolisable di-ketone substrates, and offer a potential route to decorated cyclopentanone derivatives of multiple chiral centres. Computer modelling of 1-methylbicyclo[3.3.0]octane-2,8-dione into the active site of OCH suggested that the bicyclic [3.3.0] series substrates were accommodated in the active site in similar orientation with the natural enzyme substrate, 6-oxocamphor, and would thus yield the (2S,3S)-product series.

Original languageEnglish
Pages (from-to)916-924
Number of pages9
JournalAdvanced Synthesis and Catalysis
Volume349
Issue number6
DOIs
Publication statusPublished - Apr 2007

Keywords

  • biotransformations
  • chemoenzymatic synthesis
  • ss-diketones
  • enzyme catalysis
  • enzymes
  • lyases
  • BICYCLIC BETA-DIKETONES
  • CROTONASE SUPERFAMILY
  • ENANTIOSELECTIVE SYNTHESIS
  • CRYSTAL-STRUCTURE
  • JASMONIC ACID
  • DESYMMETRIZATION
  • DIVERSITY
  • HYDROLASE
  • OXIDATION
  • LACTONES

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