Boyd Derek R, Sharma Narain D, Malone John F, McIntyre Peter B A, McRoberts Colin, Floyd Stewart, Allen Christopher C R, Gohil Amit, Coles Simon J, Horton Peter N, Stevenson Paul J
†School of Chemistry and Chemical Engineering, Queen's University of Belfast, Belfast BT9 5AG, U.K.
§Agri-food and Biosciences Institute for Northern Ireland, Belfast, BT9 5PX, U.K.
J Org Chem. 2015 Apr 3;80(7):3429-39. doi: 10.1021/jo5028968. Epub 2015 Mar 23.
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.
