Biocatalytic asymmetric oxidation

Biocatalytic asymmetric oxidation of 2,3-dihydrobenzo[. ]thiophene to (—)-(lJ)-sulfoxide in excellent yield has been reported. The enzyme used is a chloroperoxidase from the marine fungus Caldariomycesfumago. This enzyme is relatively stable and does not require any cofactor. Hydrogen peroxide was the oxygen source. Using this system, 2,3-dihydro-benzo[. ]thiophene was converted to the (—)-(i )-sulfoxide in 99.5% yield, with an ee of 99%. Similarly, 1,3-dihydro-benzo[f]thiophene could be oxidized to the corresponding sulfoxide in 80% yield <1998CH246>. 

Biocatalytic asymmetric oxidations were developed very early for key steps in the production of vitamin C [9] and steroid hormones [10] and for a series of applications in organic synthesis [8], as illustrated in Figure 20.2. The use of biocatalysts in oxidation reactions is growing [11-15] and the inherent chirality of the enzymes enables a wide variety of biocatalytic asymmetric oxidations, an overview of which is given in the next six sections. 

Figure 20.2 Historical industrial examples of biocatalytic asymmetric oxidations with oxygen.

As enantiomericaUy pure sulfoxides are excellent chiral auxUiaries for asymmetric synthesis, different approaches for biocatalytic asymmetric oxidations at the S-atom have been explored [30, 31]. Asymmetric peroxidaseorganic sulfides to sulfoxides in organic solvents opens up attractive opportunities by increased substrate solubility and diminished side reactions [32]. Plant peroxidases located in the cell wall are capable of oxidizing a broad range of structurally different substrates to products with antioxidant, antibacterial, antifungal, antiviral, and antitumor activities [33]. Hydroperoxides and their alcohols have been obtained in excellent e.e. in the biocatalytic kinetic resolution of secondary hydroperoxides with horseradish and Coprinus peroxidase [34]. 

Biocatalytic Asymmetric Oxidations with Other Enzymes... 

Many unusual biocatalytic asymmetric oxidation reactions like oxidative cychza-tion, oxidative ring expansion, oxidative deamination, or oxidative decarboxylation were discovered in the course of studies in natural product biosynthesis and the involved enzyme functions continue to be of great interest. 

Selected examples of other biocatalytic asymmetric oxidations are shown in Figure 20.10. In the area of the polyether ionophore monensin a recently proposed mechanism of oxidative cycUzation of a linear polyketide intermediate by four enzymes, the products of monBI, monBll, monCI, and monCII, has been supported experimentally by analysis of a biosynthetic gene cluster [110] and the accumulation of an B,F,F-triene, when oxidative cydization was blocked [111]. 

J341 20 Biocatalytic Asymmetric Oxidations with Oxygen... 

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