Enzyme‐Catalysed Synthesis of Cyclohex‐2‐en‐1‐one cis‐Diols from Substituted Phenols, Anilines and Derived 4‐Hydroxycyclohex‐2‐en‐1‐ones

Abstract

AbstractToluene dioxygenase‐catalysed cis‐dihydroxylations of substituted aniline and phenol substrates, with a Pseudomonas putida UV4 mutant strain and an Escherichia coli pCL‐4t recombinant strain, yielded identical arene cis‐dihydrodiols, which were isolated as the preferred cyclohex‐2‐en‐1‐one cis‐diol tautomers. These cis‐diol metabolites were predicted by preliminary molecular docking studies, of anilines and phenols, at the active site of toluene dioxygenase. Further biotransformations of cyclohex‐2‐en‐1‐one cis‐diol and hydroquinone metabolites, using Pseudomonas putida UV4 whole cells, were found to yield 4‐hydroxycyclohex‐2‐en‐1‐ones as a new type of phenol bioproduct. Multistep pathways, involving ene reductase‐ and carbonyl reductase‐catalysed reactions, were proposed to account for the production of 4‐hydroxycyclohex‐2‐en‐1‐one metabolites. Evidence for the phenol hydrate tautomers of 4‐hydroxycyclohex‐2‐en‐1‐one metabolites was shown by formation of the corresponding trimethylsilyl ether derivatives.magnified image