Enzymatic Baeyer-Villiger Oxidation

In contrast to the situation with the Baeyer-Villiger oxidation, synthetic chemists have a choice of both enzymatic or non-enzymatic methods for the oxidation of sulfides to optically active sulfoxides with good to excellent yields and enantiomeric excesses. 

Alphand, V., Furstoss, R., Pedragosa-Moreau, S., Roberts, S.M. and Willetts, A.J., Comparison of microbiologically and enzymatically mediated Baeyer-Villiger oxidations synthesis of optically active caprolactones. J. Chem. Soc. Perkin Trans. 1, 1996, 1867. 

The enzymatic Baeyer-Villiger oxidation enantioselective synthesis of lactones from mesomeric cyclohexanones, J. Am. Chem. Soc. 1988, 110, 6892-6893. 

Among the most popular oxidative biotransformations, Baeyer-Villiger monooxygenases (BVMOs) belong to the main fields of research. Nowadays, manifold enzymes catalyzing the Baeyer-Villiger oxidation are expressed in common recombinant organisms, such as E. coli or S. cerevisiae. The mechanism of the enzymatic... 

Enzymatic Baeyer-Villiger oxidations have been studied for a long time some very useful applications in natural product synthesis date back more than two decades. For example, prochiral (3A, 5,S )-4-hydroxy-3,5-dimethylcyclohexanone was successfully oxidized using a CHMO from Acinetobacter sp. NCIMB 9871. In this case the seven-membered ring formed rearranges spontaneously into the thermodynamically more stable y-lactone. The rearranged lactone has been used in the synthesis of natural products such as tirandamycin or calyculin A (Fig. 25) [157-159],... 

More recently, the formal total syntheses of some bioactive natural products bearing a tetrahydrofurane moiety were achieved by enzymatic Baeyer-Villiger oxidation using cyclopentanone monooxygenases (CPMOs) from Comamonas sp. 

Fig. 28 Enzymatic Baeyer-Villiger oxidation in the synthesis of bioactive compounds...

Gagnon R, Grogan G et al (1995) Enzymatic Baeyer-Villiger oxidations of some bicyclo [2.2.1]heptan-2-ones using monooxygenases from Pseudomonas putida NCIMB 10007 enantioselective preparation of a precursor of azadirachtin. J Chem Soc Perkin Trans 1 1505-1511... 

A Baeyer-Villiger oxidation has the potential of being asymmetric if a regioselective reaction is conducted on a meso-substrate or if a stereodifferentiated stereogenic center is already present. The oxidation can be chemical or enzymatic.213-215 216 An example of a chemical reagent in a Baeyer-Villiger reaction is provided in the synthesis of fragment A 26 from /f-carvone (27) (Scheme 9.38) as part of a synthesis of Cryptophycin A (28).217... 

When comparing chemical and biocatalytic methods, one could say that, especially for asymmetric oxidations, enzymatic methods enter the scene. This is most evident in the area of asymmetric Baeyer-Villiger oxidation, where biocatalysts take the lead and homogeneous chiral catalysts lag far behind in terms of ee values. Significant progress can be expected in the area of biocatalysis due to the advancement in enzyme production technologies and the possibility of tailor-made enzymes. 

Roberts, S.M. and Wan, P.W.H. (1998) Enzyme-catalyzed Baeyer-Villiger oxidations. Journal of Molecular Catalysis B Enzymatic, 4,111-136. 

Ottolina, G., de Gonzalo, G., Carrea, G. and Danieli, B. (2005) Enzymatic Baeyer-Villiger oxidation of bicyclic diketones. 

Figure 16.5-16. Proposed mechanisms for the enzymatic Baeyer-Villiger oxidation of cyclohexanone.

For example, the method potentially opens an access to compounds with a doubly chiral isopropyl unit (Scheme 14). In the pro-5-selective enzymatic hydroxylation of isobutyric acid (88) to (S)-/3-hydroxyisobutyric acid (89) the stereochemistry of the hydroxylation at C-3 is not known. It could be studied by preparing 88 in a doubly chiral form via stereocontrolled ami-SN2 reaction of dimethyl cuprate with the tosy-late 90 to give 91 which is then degraded by Lemieux- and then Baeyer-Villiger oxidation to 88. 

Application of dynamic kinetic resolution has also been reported in a whole-cell enzymatic Baeyer-Villiger process. While this was initially done using slightly basic conditions, Furstoss and Alphand have more recently reported the use of a weakly basic anion exchange resin to promote racemization of the slow oxidizing enantiomer 99 to the fast enantiomer 100.53 Baeyer-Villiger oxidation using recombinant E. coli to overexpress the CHMO from A. calcoaceticus provided excellent yield and % ee of lactone 101. 

Enzymatic conversion of ketones to esters is very common in microbial degradations. A synthetically important as well as typical transformation is the enzymatic Baeyer-Villiger oxidation, reported by Walsh,... 

Enzymatic Baeyer-Villiger Oxidations by Flavin Dependent Monooxygenases" Walsh. C.T. Chen, Y.-C.J. Angew. Chem. Int Ed., Engl, 1988, 27, 333. 

Olsen T, Kerton F, Marriott R et al. (2006) Biocatalytic esterification of lavandulol in supercritical carbon dioxide using acetic acid as the acyl donor. Enzyme Microb Technol 39(4) 621-625 OttoUna G, de Gonzalo G, Carrea G et al. (2005) Enzymatic Baeyer-Villiger oxidation of bicyclic diketones. Adv Synth Catal 347(7-8) 1035-104... 

Scheme 2.161 Desymmetrization of prochital ketones via enzymatic Baeyer-Villiger oxidation...

S)-4-Ethyl-e caprolactone using an enzymatic Baeyer-Villiger oxidation. The general procedure described above was also used to oxidize 4-ethylcyclohexanone (10 mmoles, 1.41 mL). In this case, an equimolar quantity of P-cyclodextrin (10 mmoles, 11.33 g) was included in the YP-Gal medium to solubilize the hydrophobic ketone. Extractive workup afforded 1.76 g of crude lactone as an orange oil. 

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