Oxygenase cyclohexanone

Branchaud BP, CT Walsh (1985) Functional group diversity in enzymatic oxygenation reactions catalyzed by bacterial flavin-containing cyclohexanone oxygenase. J Amer Chem Soc 107 2153-2161. 

Latham J, AC Walsh (1986) Retention of configuration in oxidation of a chiral boronic acid by the flavoenzyme cyclohexanone oxygenase. J Chem Soc Chem Commun 527-528. 

Related flavin hydroxylases act at nucleophilic positions on a variety of molecules393,402 including phenol,403 salicylate,404 anthranilate,405 p-c resol,406 4-hydroxyphenylacetate,407,408 and 4-aminobenzoate.409 Various microsomal flavin hydroxylases are also known 410 Flavin peroxide intermediates are also able to hydroxy late some electrophiles.411 For example, the bacterial cyclohexanone oxygenase catalyzes... 

Cyclohexanone oxygenase from Acinetobacteria converts a variety of alicyclic ketones into lactones in a regio- and enantioselective manner (Table 12). The reaction can be carried out by a whole-cell process (181) or with the isolated enzyme (178). For example, 2-norbomanone [497-38-1] (112) is converted to the corresponding lactone in 81% yield (178). The enzyme, however, is not selective both enantiomers react equally well. The oxidation rate of camphor [76-22-2] (113), is about one-third that of (112) nevertheless, given sufficient amount of time, the product yield reaches 89%. Substituted cylohexanones (114) and cyclopentanones (115) are converted into the corresponding lactones in moderate to good yield and selectivity (179—181). 

Ryerson CC, Ballou DP et al (1982) Mechanistic studies on cyclohexanone oxygenase. Biochemistry 21 2644—2655... 

The preference of cyclohexanone oxygenase for Baeyer -Villiger oxygenation vs. sulfide oxidation was tested with isomers of thiacyclohexanone. These substrates were converted by the enzyme into the corresponding lactone products with no detectable sulfoxidation 394. 

Bacterial flavoprotein monooxygenase (cyclohexanone oxygenase) has been used for the oxidation and rearrangement of allyl selenides, but the products have not been analyzed for enantiomer composition10,11. 

Chiral lactones can be formed from ketones via the Bacyer-Villiger reaction. Such lactones are potentially useful synthons for a number of natural products (37). Many of the examples of enantioselective lactone formation have been demonstrated using cyclohexanone oxygenase isolated from various Acinetobacter spedes (37,38). Figure 14 shows the enzymatic lactonization of methylcyclohexanone, which gave an 80% yield with an enantiomeric excess greater than 98%. 

A single enzyme is sometimes capable of many various oxidations. In the presence of NADH (reduced nicotinamide adenine dinucleotide), cyclohexanone oxygenase from Acinetobacter NCIB9871 converts aldehydes into acids, formates of alcohols, and alcohols ketones into esters (Baeyer-Villiger reaction), phenylboronic acids into phenols sulfides into optically active sulfoxides and selenides into selenoxides [1034], Horse liver alcohol dehydrogenase oxidizes primary alcohols to acids (esters) [1035] and secondary alcohols to ketones [1036]. Horseradish peroxidase accomplishes the dehydrogenative coupling [1037] and oxidation of phenols to quinones [1038]. Mushroom polyphenol oxidase hydroxylates phenols and oxidizes them to quinones [1039]. 

The biochemical oxidation of phenylacetaldehyde with cyclohexanone oxygenase produces phenylaeetic acid, in addition to smaller amounts of benzyl formate and benzyl alcohol (equation 351) [1034]. 

The Baeyer-Villiger reaction is also effected by biochemical oxidation using the enzyme cyclohexanone oxygenase from Acinetobacter strain NCIB 9871. Cyclohexanone is thus converted into e-caprolactone [1043], and phenylacetone (l-phenyl-2-propanone) is transformed into benzyl acetate. The formation of benzyl acetate from phenylacetone involves the same migration as that in oxidation with peroxytrifluoroacetic acid (equation 387) [1034]. More examples of biochemical Baeyer-Villiger reactions occur in diketones and steroids see equation 397). 

Phenols are also obtained by oxidation of phenylboronic acids with cyclohexanone oxygenase produced by Acinetobacter strain NCIB 9871 (equation 606) 1034. ... 

Fig. 24. Mechanism proposed for inactivation of cyclohexanone oxygenase by ethylene monothiocarbonate.

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