Enzymatic Oxygenation

Cascade Biocatalysis Integrating Stereoselective and Environmentally Friendiy Reactiom, First Edition. 

Edited by Sergio Riva and Wolf-Dieter Fessner. 

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The enzymatic oxygenation process is of particular value as there is a significant difference in the formation rates of sulfoxides and sulfones. The initial conversion of sulfide to the optically active sulfoxide by an MO is usually very fast compared to the subsequent oxidation step to sulfone, upon which chirality is lost (Scheme 9.26). In many cases, over-oxidation to sulfone is not observed at all when employing MOs. 

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. 

The stimulus for the recent surge of activity in this previously dormant area of organic chemistry can be traced to the prostaglandin connection . That is to the discovery that saturated bicyclic peroxides are key intermediates in the biosynthesis of prostaglandins and other physiologically active substances by the enzymatic oxygenation of polyunsaturated fatty acids. 

It is interesting that NADH is also required as a stoichiometric co-factor in enzymatic oxygenation processes. In a detailed study of styrene monooxygenase (StyA), Andreas Schmid of the ETH/Zurich showed (J. Am. Chem. Soc. 125 8209,2003) that Cp Rh(bpy)(H 0)fc in combination with sodium formate served effectively to regenerate the NADH. Using this combination, epoxidation of aryl alkenes such as 6, 8 and 10 proceeded in high enantiomeric... 

More recently, the degradation of a-pinene by Pseudomonas jluorescens NCIMB 11671 was described [97,98]. A novel pathway for the microbial breakdown of a-pinene (119) was proposed, Fig. (23). The attack is initiated by enzymatic oxygenation of the 1,2-double bond to form the epoxide (127). This epoxide then undergoes rapid rearrangement to produce a novel diunsaturated aldehyde, occurring as two isomeric forms. The primary product of the reaction (Z)-2-methyl-5-isopropylhexa-2,5-dien-l-al (trivial name isonovalal) (128) can undergo chemical isomerisation to the -form (novalal) (129). Isonovalal, the native form of... 

The two nitrogens in the pyrimidine structure are also likely candidates for enzymatic oxygenation. Indeed, the antibacterial agent 2,4-diamino-5-(3,4,5-trimethoxybenzyl)... 

Most enzymatic oxygenations catalyzed by monooxygenases require the presence of both molecular oxygen and an electron donor, usually referred to as the cofactor. These oxygenations are described by the general equation,... 

Recently Liu and Weller [84] have reviewed the arachidonic acid metabolism in filarial parasites and other helminths. Arachidonic acid (AA) is a 20 carbon polyunsaturated fatty acid derived from dietary fatty acids. In human tissues, AA is usually present in the esterified form such as glycerolipids, phospholipids and neutral lipids. The free AA, released by phospholipases, undergoes various enzymatic oxygenations to form local mediators such as prostaglandins and leukotrienes, which are collectively known as eicosanoids (Chart 9). These eicosanoids are associated with platelet aggregation, vasodilation, leukocyte inflammatory and immune functions and cellular adhesion [85]. 

An Enzyme-bound Red Chlorophyll Catabolite from Enzymatic Oxygenation of Pheophorbide a... 

PaO is intriguingly specific for Pheo a (5a) and is located in the chloroplast envelope. It catalyzes the remarkable transformation of 5a into (a bound form of) RCC (11) (5). Besides the incorporation of two oxygen atoms, the ring opening at the newly oxygenated sites appears to achieve, all in this step, the formation of two carbonyl functions and the saturation of the eastern (3-meso position. The mechanism of the hypothetical isomerization of the primary enzymatic oxygenation product to the ring-opened (enzyme-bound form of) 11 has not been clarified. 

Watanabe, Y, T. lyanagi, and S. Oae (1982). One electron transfer mechanism in the enzymatic oxygenation of sulfoxide to sulfone promoted by a reconstituted system with purified cytochrome P450. Tetrahedron Lett. 23, 533-536. 

Anandamide may escape metabohc degradation by FAAH through its enzymatic oxygenation. It was shown that anandamide may be metabohzed by lipoxygenases (Ueda et al., 1995 Hampson et al., 1995 Edgemond et al., 1998), COX-2 (Yu et al., 1997), or P450 hydroxylates (Bomheim et al., 1993,1995). The functional significance of such metabolic conversion is yet to be identified. 

Takata, T., Yamazaki, M., Fujimori, K., Kim, H.Y., lyanagi, T, Oae, S. (1983) Enzymatic oxygenation of sulfides with cytochrome P-450 from rabbit liver stereochemistry of sulfoxide formation. Bull. Chem. Soc. Jpn. 55, 2300-2310. 

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