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

✍ Scribed by Cheryl L. Hill; Chandra S. Verma; Gideon Grogan

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 203 KB
• Volume: 349
• Category: Article
• ISSN: 1615-4150
• DOI: 10.1002/adsc.200600468

✦ Synopsis

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 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 (2__S,3__S__)‐product series.