Enzymatic oxidation sulfoxides from

The hydridorhodium(III) species HRh(NH3)52+ and HRh(CN)4-(H20)2 are known to react with 02 to give hydroperoxide species, Rh—OOH (102, 103, 104) the sulfoxide oxidation via such an intermediate could be accommodated by several mechanisms akin to those discussed already for olefinic substrates (cf. Reactions 17 and 18). The oxidation also could occur via liberated hydrogen peroxide, which oxidizes sulfoxide to sulfone and can be formed by treatment of Rh—OOH species with acid (104). Such a mechanism would amount to a novel catalytic conversion of H2/02 mixtures to in situ H202. The part of the enzymatic cycle of P 450 that utilizes 02 and two electrons (from a hydride source) can be bypassed by using hydrogen peroxide (16, 18). 

The enzymatic oxidation of various diaryl, dialkyl, and aryl alkyl sulfides by cytochrome P-450 from rabbit liver resulted predominantly in the formation of the sulfoxides with the R-configuration[16]. 

The thioredoxin system, consisting of thioredoxin and thioredoxin reductase, was originally discovered as the hydrogen carrier system, which provides, with NADPH, the reducing potential for the reduction of ribonucleotides (5, 35). Since then considerable evidence has been accumulated to indicate that this or a closely related system also participates in a variety of other enzymatic reductions. For instance thioredoxin can function as an electron carrier between NADPH and several disulfides, such as insulin, lipoate and oxidized glutathione. Furthermore Porque et al. (114) have shown that thioredoxin and thioredoxin reductase from yeast can function as hydrogen carriers in the reduction of methionine sulfoxide and sulfate. 

Hi) Methionine Sulfoxide and Sulfone. Under controlled conditions, mild oxidizing agents convert methionine to its sulfoxide. It can also be formed by simple exposure of peptides and proteins to air for a long period of time. This derivative is unstable to acid and only partial recovery is observed after such treatment, but accurate estimates can be made from alkaline or enzymatic hydrolyses (Means and Feeney, 1971). It can also be determined by difference, a method which takes advantage of the fact that the sulfoxide does not react with alkylating agents and that sulfonium salts cannot be further oxidized to the sulfone (Neumann et a/., 1962). 

The first task was to prepare the chiral sulfoxide. The synthesis began with the conversion of methyl propionate (144) to keto-sulfide 145. Enzymatic reduction of the ketone using Baker s Yeast gave 146 with decent enantiose-lectivity. A directed oxidation of the sulfide provided an unequal mixture of sulfoxides 147 and 148 (and presumably minor amounts of material derived from the 4-5% of ent- 46 present in the starting material) from which 148 could be isolated in 50% yield. Dehydration of the alcohol provided 149 (along with some of the Z isomer). Notice that Mori decided to place the alcohol beta to the sulfoxide in the precursor of 149. There might be a number of reasons for this, but one is that it facilitated the elimination reaction (dehydration) because of the electron-withdrawing properties of the sulfoxide. 

Very recently, CPO was assessed in an enantioselective cascade oxidation using a biphasic media composed of supercritical carbon dioxide/water." Herein, the enzymatic sulfoxidation was carried out by generating hydrogen peroxide via Pd(0)-catalyzed formation from hydrogen and oxygen (in SCCO2) (Scheme 36.30). Overall, this example represents an outstanding case on how biocatalysis can be applied under different nonconventional reaction media, as... 

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