Enzyme-catalysed synthesis and absolute configuration assignments of cis-dihydrodiol metabolites from 1,4-disubstituted benzenes.
A series of ten cis-dihydrodiol metabolites has been obtained by bacterial biotransformation of the corresponding 1,4-disubstituted benzene substrates using Pseudomonas putida UV4, a source of toluene dioxygenase (TDO). Their enantiomeric excess (ee) values have been established using chiral stationary phase HPLC and 1H NMR spectroscopy. Absolute configurations of the majority of cis-dihydrodiols have been established using stereochemical correlation and X-ray crystallography and the remainder have been tentatively assigned using NMR spectroscopic methods but finally confirmed by circular dichroism (CD) spectroscopy. These configurational assignments support and extend the validity of an empirical model, previously used to predict the preferred stereochemistry of TDO-catalysed cis-dihydroxylation of ten 1,4-disubstituted benzene substrates, to more than twenty-five examples.
Boyd
Derek R
DR
School of Chemistry and Chemical Engineering, CenTACat and QUESTOR Centre, The Queen's University of Belfast, Belfast BT9 5AG, UK. dr.boyd@qub.ac.uk
Sharma
Narain D
ND
Coen
Gerard P
GP
Gray
Peter J
PJ
Malone
John F
JF
Gawronski
Jacek
J
D000429:Alcohol Oxidoreductases / Q000737:chemistry*; D001555:Benzene Derivatives / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D010105:Oxygenases / Q000737:chemistry*; D011549:Pseudomonas / Q000201:enzymology; D013237:Stereoisomerism
D001555:Benzene Derivatives; D000429:Alcohol Oxidoreductases; C023125:dihydrodiol dehydrogenases; D010105:Oxygenases; C023172:toluene dioxygenase