Oxidation enzymatic cascade reactions

P. Tanner, O. Onaca, V. Balasubramanian, W. Meier, C.G. Pahvan, Enzymatic cascade reactions inside polymeric nanocontainers a means to combat oxidative stress. Chemistry - A Enropean Jonmal 17 (2011) 4552-4560. 

In the course of developing an enzymatic cascade-reaction for the production of amines from alcohols, naftifine, a potent antifungal agent, was synthesized [148]. Cinnamyl alcohol was oxidized in a one-pot reaction with a copper-dependent galactose oxidase to the corresponding aldehyde, which was subsequently subjected to reductive amination by co-TA. AlaDH was employed to recycle the amine donor l-alanine (Figure 13.36). Ciimamylamine was produced with 92% conversion and further transformed into naftifine in 51% overall yield over four steps. 

The question of oxidative cyclization versus a polyepoxide cascade in the biosynthesis of polyether natural products has been reviewed <1995AGE298>. Enzymatic domino reactions involving epoxide intermediates have been reviewed <2001CSR332>. The DNA-damaging activity of epoxides and other oxidized species has been examined using chemical models <1995ACR289>. 

One elegant way of in situ product removal is to use the product of a first dehydrogenase reaction as substrate for a subsequent enzymatic reaction, thus recycling the oxidized nicotinamide coenzyme (Fig. 16.2-3). Various NAD(P)-de-pendent enzymes can be applied as regeneration enzymes in this cascade reaction. 

Hydrogen peroxide is not merely dismutated by catalase, but used as substrate in a second enzyme cascade reaction producing propylene oxide [123 1251. In an alternative process 1261 the reduction step was performed enzymatically using aldose reductase and formate dehydrogenase for NADH regeneration. Thus, essentially glucose free D-fructose was obtained. 

Starting from UDP-Glc/UDP-GlcNAc biocatalytic epimerization and oxidation were combined with chemical hydrazone formation. These simultaneously occurring steps may be also classified as chemo-enzymatic one-pot cascade reaction. 

The ability to perform even the simplest of muscle movement requires complex coordination of the physical and chemical activities of the tissue. In recent years, nutritionists and exercise physiologists have described how the primary energy sources in food carbohydrates, fats, and proteins are transformed into the universal "currency" of biological energy, ATP. Oxidative metabolism processes the substrates through a cascade of enzymatic events to Insure maximal efficiency in energy conversion. At every level of this conversion, one or more metal ions serve as a cofactor to facilitate these biochemical reactions. The requirement of metals in the production of... 

As indicated by the reaction steps (9), (10), and (11), oxidants, namely O ", H O, and OH are intermediate products of the enzymatically controlled cascade. Their reactivity and presnmable site of action can be assessed by physico-chemical parameters, such as standard reduction potential ( ) and half-life (tj j) of the given species (cf Table 4). 

The combination of a chemoselective enzymatic reduction step with another second enzymatic reaction is another opportunity to overcome limitations, for example, in the case of the enantiosdective reduction of prochiral unsaturated aldehydes by coupling a reduction step with an isolated ene reductase (OYE 2 or OYE3) together with an oxidation step with HLADH in a cascade system, which allowed both yields and enantioselectivities to be improved [136]. 

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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