Sulfoxide reductions

The reduction of sulfoxides is a two-electron transfer process that results in the formation of thioethers. 

The environmental significance of organic sulfoxides results primarily from their importance as agrochemicals specifically, the organophosphorus and carbamate insecticides containing sulfoxide moieties. Studies suggest that reduction of these chemicals can be the primary pathway for their transformation in anoxic sediments. For example, reduction of phorate sulfoxide to phorate in anoxic pond sediments occurred with half-lives ranging from 2 to 41 days (Equation 3.38) (Tratnyek and Wolfe, 1988). 

Oxidation of phorate back to phorate sulfoxide was not observed in these systems. Because only a small portion of phorate sulfoxide was sorbed to the sediment, sorption did not have a significant effect on the reduction kinetics. As is often the case, removal of the sediment phase by filtration inhibited reduction, suggesting that the reducing agent was sediment associated. Studies in heat-sterilized and amended sediments suggested that the reduction of phorate sulfoxide was due to extracellular soil enzymes or microbial cometabolism. 

The reduction of aldicarb sulfoxide, which is the major metabolite in aerobic soils, has been observed in groundwater systems (Miles and Delfino, 1985 Lightfoot et al., 1987). 

An understanding of the factors that control the redox equilibria for aldicarb and aldicarb-sulfone is important because hydrolysis of aldicarb-sulfoxide will occur at a much faster rate than hydrolysis of aldicarb. 

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This group was developed for the protection of primary amides of amino acids. It is introduced by amide bond formation with the benzhydrylamine. It is cleaved with 1 MSiCl4/anisole/TFA/0° or 1 MTMSOTf/thioanisole/TFA, 0°. Cleavage occurs by initial sulfoxide reduction followed by acidolysis. ... 

The sulfoxide directed reduction of olefin is known, so is sulfoxide reduction by chloroborane, but not simultaneous reduction of both by borane. 

To gain understanding of the interdependence between the olefin reduction and the sulfoxide reduction, the saturated sulfoxide 52 was prepared and treated with BH3-THF. No reaction was observed under the similar conditions (Scheme 5.18). The unactivated vinyl sulfide 16 was also not reactive toward BH3-THF. These results indicated that sulfoxide and olefin were reduced simultaneously, not independently. Again this phenomenon was unexpected and pointed to the unique nature of this reaction. 

Reductions Epoxide hydroplase Azo and nitro reduction Carbonyl reductase Disulfide reduction Sulfoxide reduction Quinone reduction Reductive dehalogenation Microsomes, cytosol Gut microflora Cytosol Cytosol Cytosol Cytosol, microsomes Microsomes... 

Sulfoxide Reduction Sulfoxide reduction is a two-electron-transfer reversible reaction resulting in thioethers. Organic sulfoxides are used mainly as agrochemicals, and their reduction (abiotic and microbially mediated) has been found in anaerobic soils, sediments, and groundwater (Larson and Weber 1994). 

Reduction reactions mediated by microorganisms may include the reduction of nitro bonds, sulfoxide reduction, and reductive dehalogenation. Reduction of the nitro group to amine involves the intermediate formation of nitrase and hydroxy amino groups. Selected reductive reactions may involve the saturation of double bonds, reduction of aldehydes to alcohols or ketones to secondary alcohols, or of certain metals. The main reductive processes in the subsurface environment have been discussed earlier in this chapter. 

In the reaction of the a-lithio sulfoxides, reduction of sulfinyl-substituted products is performed with potassium hydride.52 Selected examples of this reaction are given in Table 5, for further examples see ref 52. 

Griebler, C., and D. Slezak, Microbial activity in aquatic environments measured by dimethyl sulfoxide reduction and intercomparison with commonly used methods , Appl. Environ. Microbiol., 67,100-109 (2001). 

Sulfonium salts of thiepanes are readily formed by electrophilic attack of alkyl halides on the cyclic thioether. Thus, thiepane (35) was found to yield a sulfonium iodide (123), which at elevated temperatures and in the presence of excess methyl iodide underwent ring cleavage to yield 1,6-diiodohexane (isolated as the 1,6-diphenoxy derivative Scheme 24) (53M1206). The alkoxysulfonium salt (124) formed by reaction of (35) with t-butyl hypochlorite (equation 23) was characterized as a stable hexachloroantimonate (67JOC2014). Reduction of thiepane 1-oxide (115) to thiepane has been achieved using an aqueous solution of NaHSC>3 (72JOC919). A hydroxysulfonium salt intermediate (125) has been proposed in the latter reduction reaction which provides a general method for sulfoxide reductions under mild conditions (equation 24). 

Sulfoxide Reduction. The reduction of sulfoxides has been reported to occur in mammalian tissues. Soluble thioredoxin-dependent enzymes in the liver are responsible in some cases. It has been suggested that oxidation in the endoplasmic reticulum followed by reduction in the cytoplasm may be a form of recycling that could extend the in vivo half-life of certain toxicants. 

A number of functional groups, such as nitro, diazo, carbonyls, disulfides, sulfoxides, and alkenes, are susceptible to reduction. In many cases it is difficult to determine whether these reactions proceed nonenzymatically by the action of biological reducing agents such as NADPFI, NADH, and FAD or through the mediation of functional enzyme systems. As noted above, the molybdenum hydroxylases can carry out, in vitro, a number of reduction reactions, including nitro, azo, A-oxidc, and sulfoxide reduction. Although the in vivo consequences of this are not yet clear, much of the distribution of reductases described below may be, in whole or in part, the distribution of molybdenum hydroxylases. 

C2-symmetric cyclic alkenyl sulfoxide (187), with cyclopentadiene, proceeded under mild conditions to give a single diastereomeric adduct (188) in excellent yield (Scheme 48). Other acyclic dienes also gave single diastereomeric adducts often without the necessity of using Lewis acids. The Ws-sulfoxide moiety can be readily deprotected using a two-step sequence of sulfoxide reduction followed by hydrolysis of the dithiolane to give the enantiomerically pure norbomenone (189). 

Cyclic sulfoxides, reduction into sulfides 88T6537. 

Zinder S. H. and Brock T. D. (1978b) Dimethyl sulfoxide reduction by microorganisms. J. Gen. Microbiol. 105,... 

Sulindac Sulfide metabolite of sulindac Sulfoxide reduction... 

Formation of sulfide with concurrent ester hydrolysis was achieved when various Cj cyclopropyl cephalosporin 5-oxide 2,2,2-trichloroethyl esters were treated with phosphorus trichloride followed by zinc under acidic conditions. Sulfoxide reduction also occurred on treatment of cyclopropyl phenyl sulfoxide with a mixture of benzenethiol and chlorotrimethylsilane in chloroform to give cyclopropyl phenyl sulfide in 76% yield and on reaction of various substituted cyclopropyl phenyl sulfoxides with diisobutylaluminum hydride. ... 

Sulfoxide Reduction. Reduction of the sulfoxide of the mercapturic acid of 2-chloro-f+-isopropylacetanilide by Intestinal microflora has been shown in vitFo (9), but has not been demonstrated to occur in tissues. The excretion of this mercapturate sulfoxide, which is excreted into the intestine with the bile, in feces from germfree rats dosed with the acetanilide is vivo evidence for the reductive function of the intestinal microflora (49) in MftP catabolism. This reduction, in addition to deacetylation, is another source for cysteine conjugates which can be translocated to the tissues for metabolism or excretion, or remain in the intestine and further catabolized by the microflora. 

Union of the two segments was now effected via formation of the dianion of 208 and subsequent addition to ketone 202 to afford 209 in 80% yield. Although contaminated with a small amount of the C-6 epimer (ratio 5 1), the major component 209 contained all the necessary carbon atoms and possessed the required stereochemistry (except the C-13 alcohol) for the completion of erythronolide A. To this end, the methylene group was ozonolyzed, and the sulfoxide reductively cleaved, providing ketone 210 (84%). Stereoselective reduction of the ketone concomitant with cleavage of the silyl ether gave an 85% yield of 211 as a 20 1 mixture of C-13 Isomers. Intermediate 211 contains all the stereochemical centers present in erythronolide A. 

Sulfoxide reduction. By using this reagent to reduce sulfoxides, many functional groups (e.g., esters, carbamates) are not affected. 

Sulfoxide reduction In the presence of MeaS sulfoxides are reduced in very high yields to sulfides. This process as a followup reaction to sulfinylethylation of cyclic ketones is synthetically useful. 

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