Enantioselective Sulfoxidation Catalyzed by Vanadium Haloperoxidases

Abstract

Vanadium haloperoxidases catalyze the oxidation of halides by hydrogen peroxide to produce hypohalous acid. We demonstrate that these enzymes also slowly mediate the enantioselective oxidation of organic sulfides (methyl phenyl sulfide, methyl p-tolyl sulfide, and 1-methoxy-4 (methylthio)benzene) to the corresponding sulfoxides (turnover frequency 1 min(-)(1)). The vanadium bromoperoxidase from the brown seaweed Ascophyllum nodosum converts methyl phenyl sulfide to the (R)-enantiomer of the sulfoxide (55% yield and 85% enantiomeric excess (ee)). At low peroxide concentrations a selectivity of 91% can be attained. The enzyme catalyzes the selective sulfoxidation reaction over a broad pH range with an optimum around pH 5-6 and remains completely functional during the reaction. When the vanadium bromoperoxidase from the red seaweed Corallina pilulifera is used the (S)-enantiomer (18% yield and 55% ee) is formed. In contrast, the vanadium chloroperoxidase from the fungus Curvularia inaequalis catalyzes the production of a racemic mixture (54% yield), which seems to be an intrinsic characteristic of this enzyme.

A vanadium‐51 NMR study of the binding of vanadate and peroxovanadate to proteins

“…3 These enzymes catalyse the oxidation of halide to hypohalous acid and of (prochiral) sulfides to (chiral) sulfoxides by peroxide [Eqns (1) and (2)]. 4,5 Vanadate is covalently attached to the protein via a histidine and a tight hydrogen bonding network involving water and amino acid side-chains.…”

Modelling the Sulfoxygenation Activity of Vanadate‐Dependent Peroxidases

“…3 Pr)] under homogenous conditions, in chlorinated hydrocarbons at 08 for the sulfoxygenation of thioanisol (Scheme 1), using cumyl hydroperoxide as the oxidant. The results are collated in Table 4, where [V] in Entries 1 -3 stands for the essentially ligand-free V complex, i.e., OV(OSi) 3 , formed as the Table 4).…”

“…These complexes also mimic the sulfoxygenation activity of VHPOs, i.e., sulfides are oxidized to sulfoxide and some sulfone. 3 ]. Both in homogeneous and heterogeneous catalysis of the sulfoxygenation of thioanisol, optically active induction is modest.…”

“…For the homogeneous systems, this is likely due to flexibility of the active catalyst, a peroxo complex of composition [VO(L)(OOCm)] (Cm ¼ cumyl). In heterogeneous catalysis, the low ee value is presumably due to rearrangement of the complexes [VO(L)(OR)] in the silica matrix, i.e., (partial) formation of O¼V(OSi) 3 , a rearrangement which can be circumvented when using less reactive supports, such as Merrifield or Barlos resins [17]. The most efficient system with respect to selectivity (yield of the sulfoxide) and turnover is the aggregated catalyst, [VO(…”

The rational design of semisynthetic peroxidases

“…Unfortunately, the active site of vanadium-dependent haloperoxidases can accommodate only very small substrates, such as halide ion, which severely curtails their utility. Nevertheless, enantioselective sulfoxidation was catalyzed by vanadium-dependent bromoperoxidases from Corallina officinalis (Andersson et al, 1997) and Ascophyllum nodosum (Ten Brink et al, 1998). Recently, it was established (Hemrika et al, 1997;Neuwald, 1997) that vanadium chloroperoxidases are structurally closely related to the (membranebound) acid phosphatases, and the apoenzyme of vanadium chloroperoxidase was shown to exhibit phosphatase-like activity.…”