Dioxygenase-catalysed oxidation of alkylaryl sulfides: sulfoxidation versus cis-dihydrodiol formation

Abstract

Toluene- and naphthalene-dioxygenase-catalysed sulfoxidation of nine disubstituted methylphenyl sulfides, using whole cells of Pseudomonas putida, consistently gave the corresponding enantioenriched sulfoxides. Using the P. putida UV4 mutant strain, and these substrates, differing proportions of the corresponding cis-dihydrodiol sulfides were also isolated. Evidence was found for the concomitant dioxygenase-catalysed cis-dihydroxylation and sulfoxidation of methyl para-tolyl sulfide. A simultaneous stereoselective reductase-catalysed deoxygenation of (S)-methyl para-tolyl sulfoxide, led to an increase in the proportion of the corresponding cis-dihydrodiol sulfide. The enantiopurity values and absolute configurations of the corresponding cis-dihydrodiol metabolites from methyl ortho- and para-substituted phenyl sulfides were determined by different methods, including chemoenzymatic syntheses from the cis-dihydrodiol metabolites of para-substituted iodobenzenes. Further evidence was provided to support the validity of an empirical model to predict, (i) the stereochemistry of cis-dihydroxylation of para-substituted benzene substrates, and (ii) the regiochemistry of cis-dihydroxylation reactions of ortho-substituted benzenes, each using toluene dioxygenase as biocatalyst.

Enzyme‐Catalysed Synthesis and Absolute Configuration Assignments of cis‐Dihydrodiol Metabolites from 1,4‐Disubstituted Benzenes

“…These include stereochemical correlation, [15] X-ray crystallography, [30,31] and 1 H NMR analysis of di-MTPA esters [31,32] or chiral boronates. [16,33] Unfortunately the chromatographic methods (CSPHPLC and CSPGC) did not give information on the absolute configuration and the NMR methods (di-MTPA esters and chiral boronates), and early CD studies [34] provided only tentative assignments.…”

“…The simplest literature method used for the direct determination of enantiopurity of benzene cis-dihydrodiols is chiral stationary phase HPLC (CSPHPLC) at ambient temperature. [13,16] Chiral stationary phase GC (CSPGC) has also been used but this required the formation of n-butyl boronate derivatives and elevated temperatures. [28,29] Comparison of optical rotations, and in some cases X-ray crystallographic analysis, [30,31] of cis-dihydrodiols and derivatives, has also been used to confirm their enantiopurity.…”

“…[15] This model has recently been updated to also allow predictions for substrates bearing substituents which are non-spherically symmetrical and whose size will be conformationally dependent but which have a dominant stereodirecting effect, for example, SMe, [16] CH=CH 2 , [17] Et, [18] Pr. [18] With increasing use now being made of disubstituted benzene cis-dihydrodiols as chiral precursors in synthesis, [19][20][21][22][23][24][25][26][27] the development of more convenient and rigorous methods for stereochemical assignment is very important.…”

Structure, Function, and Mechanism of the Phenylacetate Pathway Hot Dog-fold Thioesterase PaaI

“…The enzymes that make up the aromatic catabolic pathways are useful for bioremediation of environmental aromatic pollutants (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) and for chemical synthesis (3,(12)(13)(14)(15). Studies of the aromatic pathways operative in common bacteria such as Escherichia coli and Pseudomonas putida (16,17) have provided a framework against which novel pathways of environmental bacteria can be understood (18,19).…”

Aerobic Degradation of Mercaptosuccinate by the Gram-Negative BacteriumVariovorax paradoxusStrain B4

“…These later studies demonstrated that sulfoxidation reactions are common steps during oxidation of various sulfides. Different classes of enzymes are involved in these processes (2, 9, 37), including those initially not related to the metabolism of OSCs (8,26,46). Concerning Mo-dependent enzymes, two members of DMSO reductase family are also able to catalyze the oxidation of OSCs.…”