Sulfoxidation enzyme-catalyzed

Figure 4.7 Example of the effect of dimethyl sulfoxide (DMSO) concentration on the initial velocity of an enzyme-catalyzed reaction.

Enantiomerically pure sulfoxides play an important role in asymmetric synthesis either as chiral building blocks or stereodirecting groups [156]. In the last years, metal- and enzyme-catalyzed asymmetric sulfoxidations have been developed for the preparation of optically active sulfoxides. Among the metal-catalyzed processes, the Kagan sulfoxidation [157] is the most efficient, in which the sulfide is enantioselectively oxidized by Ti(OzPr)4/tBuOOH in the presence of tartrate as chirality source. However, only alkyl aryl sulfides may be oxidized by this system in high enantiomeric excesses, and poor enantioselectivities were observed for dialkyl sulfides. 

As shown in Table 12,H202 and fBuOOH have been used frequently as oxygen donors in peroxidase-catalyzed sulfoxidations. Other achiral oxidants, e.g. iodo-sobenzene and peracids, are not accepted by enzymes and, therefore, only racemic sulfoxides were found (c.f. entries 34-36). Interestingly, racemic hydroperoxides oxidize sulfides to sulfoxides enantioselectively under CPO catalysis [68]. In this reaction, not only the sulfoxides but also the hydroperoxide and the corresponding alcohol were produced in optically active form by enzyme-catalyzed kinetic resolution (cf. Eq. 3 and Table 3 in Sect. 3.1). 

This enzyme [EC 4.4.1.4], also known as alliinase and cysteine sulfoxide lyase, catalyzes the conversion of an 5-alkyl-L-cysteine 5-oxide to an alkyl sulfenate and 2-aminoacrylate. The enzyme requires pyridoxal phosphate. 

The enzyme-catalyzed stereoselective oxidations of 1,2-dithiane and l,4-dihydro-2,3-benzodithiin were also investigated <2002CC1452>. Using naphthalene dioxygenase and chloroperoxidase, enantiomerically enriched sulfoxides (1,2-dithiane 1-oxides) were obtained l,4-dihydro-2,3-benzodithiin yielded a product of 32—47% ee with an excess of the (6)-configuration while 1,2-dithiane yielded almost enantiopure (96% ee) (R)-configured 1-oxide. Finally, 1,4-dihydro-2,3-benzodithiin 2-oxide was also prepared by perborate oxidation <1988JOC2608>. 

Within the present article, a few selected examples are provided ofboth classical and more recent glycosylation methods applied to the synthesis of sLcL sLe", or of sulfated Lewis determinants. Recent procedures involve the use of glycal donors as developed by Danishefsky and his associates, of glycosyl fluorides according to Mukaiyama and Nicolaou, of sulfoxide donors as reported by Kahne, and enzyme-catalyzed oligosaccharide syntheses as developed by the schools of Whitesides, Wong, and Paulson. ... 

Comparatively, less-studied system is the peroxidase-catalyzed oxidations. One such example is the enantioselective oxidation of phenylmethylsulfide catalyzed by chloroperoxidase from Caldariomyces fumago in several buffer-IL mixtures at different pH values (Scheme 10.12) [107]. In this case, the chloroperoxidase-catalyzed sulfoxidation showed 70% product yield and above 99% ee, in ILs like [MMIM] [Me2P04] and cholinium acetate and cholinium citrate. But for the same sulfoxidation reaction catalyzed by chloroperoxidase, complete loss of enzyme activity was observed in morpholine containing ILs and [MMIM][MeSOJ [107]. The authors have pointed out that the addition of IL to the reaction medium influences the pH level and enzyme activity. For example, addition of 30% (vol/vol) [MMIM] [Me PO J increases the pH of a potassium phosphate buffer solution from 2.7 to 3.7. Enzyme activity of chloroperoxidase was significantly reduced at pH 2.7 which was recovered by increasing the pH to 3.7. (Note The authors have chosen potassium... 

Oxidations/hydroxylations of linactivated saturated carbons (polyunsaturated) fatty acids epoxidation and dihydroxylation of alkenes aromatic compounds (- unsaturated diols) hydroxylated compounds and aldehydes diols (and lactonization) enzyme catalyzed Baeyer-Villiger oxidations organic sulfides (sulfoxidation) Be, Mi, Mp, Po, Ra, CytP450 enzymes, monooxygenases SLO An, Nc, Po Pp (mutant strain), Ce Go, Ps Bp, Go, Ko, Ps, HLADH Ac, Ps, CHO BY, An, Ceq, Mi, Po, CPO, BSA... 

The nonlinear optical (NLO) susceptibilities of bioengineered aromatic polymers synthesized by enzyme-catalyzed reactions are given in Tables 2, 3, and 4. Homopolymers and copolymers are synthesized by enzyme-catalyzed reactions from aromatic monomers such as phenols and aromatic amines and their alkyl-substituted derivatives. The third-order nonlinear optical measurements are carried out in solutions at a concentration of 1 mg/mL of the solvent. Unless otherwise indicated, most of the polymers are solubilized in a solvent mixture of dimethyl formamide and methanol (DMF-MeOH) or dimethyl sulfoxide and methanol (DMSO-MeOH), both in a 4 1 ratio. These solvent mixtures are selected on the basis of their optical properties at 532 nm (where all the NLO measurements reported here are carried out), such as low noise and optical absorption, and solubility of the bioengineered polymers in the solvent system selected. To reduce light scattering, the polymer solutions are filtered to remove undissolved materials, the polymer concentrations are corrected for the final x calculations, and x values are extrapolated to the pure sample based on the concentrations of NLO materials in the solvent used. Other details of the experimental setup and calculations used to determine third-order nonlinear susceptibilities were given earlier and described in earlier publications [5,6,9,17-19]. 

Auret, B.J., Boyd, D.R., Breen, R and Grene, R.M.E. and Robinson, P.M. (1981) Stereoselective enzyme-catalyzed oxidation-reduction of thioacetals-thioacetal sulfoxides by fungi. /. Chem. Soc. Perkin Trans. 1, 930-933. 

The high-valent iron-oxo sites of nonheme iron enzymes catalyze a variety of reactions (halogenation and hydroxylation of alkanes, desaturation and cyclization, electrophilic aromatic substitution, and cis-dihydroxylation of olefins) [lb]. Most of these (and other) reactions have also been achieved and studied with model systems [Ic, 2a-c]. With the bispidine complexes, we have primarily concentrated on olefin epoxidation and dihydroxylation, alkane hydroxylation and halogenation, and sulfoxidation and demethylation processes. The focus in these studies so far has been on a thorough analysis of the reaction mechanisms rather than the substrate scope and catalyst optimization. 

Biologically, the reduction of methionine sulfoxide to methionine with NADPH is catalyzed by an enzyme . Recently, the mechanism of reduction of sulfoxides by treatment with an NADPH model has been studied . 

Although UGTs catalyze only glucuronic acid conjugation, CYPs catalyze a variety of oxidative reactions. Oxidative biotransformations include aromatic and side chain hydroxylation, N-, O-, S-dealkylation, N-oxidation, sulfoxidation, N-hydroxylation, deamination, dehalogenation and desulfation. The majority of these reactions require the formation of radical species this is usually the rate-determining step for the reactivity process [28]. Hence, reactivity contributions are computed for CYPs, but a different computation is performed with the UGT enzyme (as described in Section 12.4.2). 

Enzymes, in particular peroxidases, catalyze efficiently the enantioselective oxidation of alkyl aryl sulfides and also dialkyl sulfides, provided that the alkyl substituents are sterically differentiable by the enzyme. The peroxidases HRP, CPO, MP-11, and the mutants of HRP, e. g. F41L and F4IT, were successfully used as biocatalysts for the asymmetric sulfoxidation (Eq. 14). A selection of sulfides. 

Peroxidases have been used very frequently during the last ten years as biocatalysts in asymmetric synthesis. The transformation of a broad spectrum of substrates by these enzymes leads to valuable compounds for the asymmetric synthesis of natural products and biologically active molecules. Peroxidases catalyze regioselective hydroxylation of phenols and halogenation of olefins. Furthermore, they catalyze the epoxidation of olefins and the sulfoxidation of alkyl aryl sulfides in high enantioselectivities, as well as the asymmetric reduction of racemic hydroperoxides. The less selective oxidative coupHng of various phenols and aromatic amines by peroxidases provides a convenient access to dimeric, oligomeric and polymeric products for industrial applications. 

This pyridoxal-phosphate-dependent enzyme [EC 4.4.1.13] catalyzes the conversion of an 5-substituted cysteine (that is, RS-CH2-CH(NH3")C00 ) to RSH, ammonia, and pyruvate. See also S-Substituted Cysteine Sulfoxide Lyase... 

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