The production and synthetic utility of the dioxygenase-derived metabolites of substituted aromatics

Abstract

The substrate scope and selectivity of toluene dioxygenase overexpressed in E.coli JM109 (pDTG601A) was investigated with series of ortho-halobenzoates and para-substituted arenes. Palladium-catalyzed carbonylation methodology was developed to convert halogenated cis-dihydrodiol metabolites to the corresponding carboxylates and a comparison of the overall efficiency between the enzymatic and chemical methods of access was made. Some of the metabolites produced by toluene dioxygenase were employed in a synthetic approach toward tetrodotoxin. Enzymatic dihydroxylation of benzoic acid with R. eutropha B9 provided the corresponding ipso-diol that was used in the first total synthesis of pleiogenone A, a bioactive natural product. Experimental and spectral data are provided for all new compounds.