Desymmetrisations of 1-Alkylbicyclo[3.3.0]octane-2,8-diones by Enzymatic Retro-Claisen Reaction Yield Optically Enriched 2,3-Substituted Cyclopentanones

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 diketone 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.