title: Toluene dioxygenase-catalyzed synthesis and reactions of cis-diol metabolites derived from 2- and 3-methoxyphenols.
abstract: Using toluene dioxygenase as biocatalyst, enantiopure cis-dihydrodiol and cis-tetrahydrodiol metabolites, isolated as their ketone tautomers, were obtained from meta and ortho methoxyphenols. Although these isomeric phenol substrates are structurally similar, the major bioproducts from each of these biotransformations were found at different oxidation levels. The relatively stable cyclohexenone cis-diol metabolite from meta methoxyphenol was isolated, while the corresponding metabolite from ortho methoxyphenol was rapidly bioreduced to a cyclohexanone cis-diol. The chemistry of the 3-methoxycyclohexenone cis-diol product was investigated and elimination, aromatization, hydrogenation, regioselective O-exchange, Stork-Danheiser transposition and O-methylation reactions were observed. An offshoot of this technology provided a two-step chemoenzymatic synthesis, from meta methoxyphenol, of a recently reported chiral fungal metabolite; this synthesis also established the previously unassigned absolute configuration.
authors.affiliation: †School of Chemistry and Chemical Engineering, Queen's University of Belfast, Belfast BT9 5AG, U.K.
authors.forename: Derek R
authors.initials: DR
authors.lastname: Boyd
authors.affiliation: †School of Chemistry and Chemical Engineering, Queen's University of Belfast, Belfast BT9 5AG, U.K.
authors.forename: Narain D
authors.initials: ND
authors.lastname: Sharma
authors.affiliation: †School of Chemistry and Chemical Engineering, Queen's University of Belfast, Belfast BT9 5AG, U.K.
authors.forename: John F
authors.initials: JF
authors.lastname: Malone
authors.affiliation: †School of Chemistry and Chemical Engineering, Queen's University of Belfast, Belfast BT9 5AG, U.K.
authors.forename: Peter B A
authors.initials: PB
authors.lastname: McIntyre
authors.affiliation: §Agri-food and Biosciences Institute for Northern Ireland, Belfast, BT9 5PX, U.K.
authors.forename: Colin
authors.initials: C
authors.lastname: McRoberts
authors.affiliation: §Agri-food and Biosciences Institute for Northern Ireland, Belfast, BT9 5PX, U.K.
authors.forename: Stewart
authors.initials: S
authors.lastname: Floyd
authors.affiliation: ‡School of Biological Sciences, Queen's University of Belfast, Belfast, BT9 5AG, U.K.
authors.forename: Christopher C R
authors.initials: CC
authors.lastname: Allen
authors.affiliation: ‡School of Biological Sciences, Queen's University of Belfast, Belfast, BT9 5AG, U.K.
authors.forename: Amit
authors.initials: A
authors.lastname: Gohil
authors.affiliation: ∥National Crystallography Service, School of Chemistry, University of Southampton, Southampton, SO17 1BJ, U.K.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Coles
authors.affiliation: ∥National Crystallography Service, School of Chemistry, University of Southampton, Southampton, SO17 1BJ, U.K.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Horton
authors.affiliation: †School of Chemistry and Chemical Engineering, Queen's University of Belfast, Belfast BT9 5AG, U.K.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Stevenson
mesh_terms: D055162:Biocatalysis; D001711:Biotransformation; D018360:Crystallography, X-Ray; D003512:Cyclohexanones / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C000604154:3-methoxycyclohexenone; D003512:Cyclohexanones; D007659:Ketones; D009281:Naphthalenes; D010636:Phenols; C507866:trans-1,2-dihydro-1,2-naphthalenediol; D010105:Oxygenases; C023172:toluene dioxygenase