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On the Resolution of Chiral Substrates by a retro‐ Claisenase Enzyme: Biotransformations of Heteroannular Bicyclic β‐Diketones by 6‐Oxocamphor Hydrolase
Author(s) -
Hill Cheryl L.,
Hung Lee Chiang,
Smith Derek J.,
Verma Chandra S.,
Grogan Gideon
Publication year - 2007
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200700046
Subject(s) - bicyclic molecule , chemistry , stereochemistry , kinetic resolution , nonane , diketone , cyclopentanone , octane , enantioselective synthesis , organic chemistry , catalysis
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 β‐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‐2,8‐diones, 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 1‐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‐allylhexahydroindene‐1,7‐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‐methyloctahydrobenzocycloheptene‐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.