Enzymatic transformations oxidations

An interesting combination of enzymatic with non-enzymatic transformation in a one-pot three-step multiple sequence was reported by Waldmann and coworkers [82]. Phenols 125 in the presence of oxygen and enzyme tyrosinase are hydroxylated to catechols 126 which are then oxidized in situ to ortho quinones 127. These intermediates subsequently undergo a Diels-Alder reaction with inverse electron demand by reaction with different dienophiles (Table 4.19) to give endo bicyclic 1,2-diketones 128 and 129 in good yields. 

Remarkably, alkanes are oxidatively transformed by biological organisms at benign temperatures and pressures. Clearly, enzymatic transformations of alkanes and their well studied mechanisms (e.g., for cytochrome P450) are beyond the... 

Scheme 5. Proposed biosynthesis of allene oxide 64 from 8i -lipoxygenase initiated metabolism of arachidonic acid and subsequent non-enzymatic transformations to racemic cyclopenteone 30 [86]...

Enzymatic transformations of alkaloids by peroxidases most probably occur by single-step oxidations catalyzed by the HRP-I and HRP-II forms of the enzyme. The catalysis of one-electron oxidations of compounds containing aromatic hydrocarbon, hydrazine, phenol, hydroxamic acid, and amine functional groups has been recently reviewed (45, 58, 82). A brief summary of those HRP reactions that involve functional groups most commonly occurring in alkaloids is presented below. 

Recent work in our laboratories has confirmed the existence of a similar pathway in the oxidation of vindoline in mammals (777). The availability of compounds such as 59 as analytical standards, along with published mass spectral and NMR spectral properties of this compound, served to facilitate identification of metabolites formed in mammalian liver microsome incubations. Two compounds are produced during incubations with mouse liver microsome preparations 17-deacetylvindoline, and the dihydrovindoline ether dimer 59. Both compounds were isolated and completely characterized by spectral comparison to authentic standards. This work emphasizes the prospective value of microbial and enzymatic transformation studies in predicting pathways of metabolism in mammalian systems. This work would also suggest the involvement of cytochrome P-450 enzyme system(s) in the oxidation process. Whether the first steps involve direct introduction of molecular oxygen at position 3 of vindoline or an initial abstraction of electrons, as in Scheme 15, remains unknown. The establishment of a metabolic pathway in mammals, identical to those found in Strep-tomycetes, with copper oxidases and peroxidases again confirms the prospective value of the microbial models of mammalian metabolism concept. 

In MET, a low-molecular-weight, redox-active species, referred to as a mediator, is introduced to shuttle electrons between the enzyme active site and the electrode.In this case, the enzyme catalyzes the oxidation or reduction of the redox mediator. The reverse transformation (regeneration) of the mediator occurs on the electrode surface. The major characteristics of mediator-assisted electron transfer are that (i) the mediator acts as a cosubstrate for the enzymatic reaction and (ii) the electrochemical transformation of the mediator on the electrode has to be reversible. In these systems, the catalytic process involves enzymatic transformations of both the first substrate (fuel or oxidant) and the second substrate (mediator). The mediator is regenerated at the electrode surface, preferably at low overvoltage. The enzymatic reaction and the electrode reaction can be considered as separate yet coupled. 

The presence of diacetyl at any stage of the process does not necessarily indicate an infection by pediococci, because diacetyl is normally formed during fermentation by oxidation of the precurser 2-acetolactate, which reaches a peak (1—1.2 ppm) at 24—36 h fermentation. The concentration of 2-acetolacetate is usually reduced to values of 0.01 ppm or less, and the diacetyl is reabsorbed by the yeast cells and enzymatically transformed through acetoin to butanediol. It is extremely important that 2-acetolactate as diacetyl is reduced below the threshold of 0.05—0.10 ppm (in terms of diacetyl). 

A number of oxidation reactions of mono- and difluorosteroid compounds has been reported. In some reactions, the specific influence of a fluoro substituent on the reactivity has been observed the presence of a 9a-fluorine in a 11 /i-hydroxy-A4-3-oxo steroid causes completely stcreospecific alkaline epoxidation with hydrogen peroxide in a much slower reaction (4d vs 4 h) in comparison with the nonfluorinated analog.322 Most oxidations are accomplished by the highest selective biochemical (that is, by bacterial enzymatic) transformations. As the biochemical oxidation systems are not discussed in this section, only a list of selected transformations of steroids is presented in Table 21. For additional information see ref 323. 

For further degradation of RCO—SCoA, it first must be oxidized to a /3-keto thioester. The reactions that accomplish this oxidation are shown in Figure 18-8 and involve a sequence of enzymatic transformations of the type... 

Fig. 14.12. Enzymatic transformation of acyclic squalene oxide (A) into tetracyclic lano-sterol (G). The oxidosqualene-lanosterol cyclase controls the conformation of the substrate so effectively that only one out of 64 possible diastereomers is formed.

Davila et al. [68] reported the transformation of the pesticides bromoxynil, dichlorophen, and pentachlorophenol by the versatile peroxidase from B. adusta. For the three transformed pesticides by versatile peroxidase, an oxidative dehalo-genation was observed, a very important process since the halogenated pesticides are considered more persistent and toxic than the organophosphorus pesticides, because of the carbon-halogen bond. Enzymatic transformation of dichlorophen compound... 

There are many reactions in soil-water systems pertaining to nutrient availability, contaminant release, and nutrient or contaminant transformations. Two processes regulating these reactions are chemical equilibria (Chapter 2) and kinetics. The specific kinetic processes that environmental scientists are concerned with include mineral dissolution, exchange reactions, reductive or oxidative dissolution, reductive or oxidative precipitation, and enzymatic transformation. This chapter provides a quantitative description of reaction kinetics and outlines their importance in soil-water systems. 

A multifunctional biosynthetic machinery mediates the synthesis of these complex natural products from acetyl- and propionyl-coenzyme A [3). In the case of type I polyketide-synthases, the )8-oxo-esters made by polycondcnsa-tion steps are modified for example by reduction or dehydration after the chain elongation. Additional specific enzymatic transformations, e.g. oxidations and glycosylations, usually take place after the decoupling at the completed macrocyclic ring framework [1,3],... 

The tetrapyrroles 31 and epi-31 were suggested to arise from further endogenous (yet possibly non-enzymatic) transformation of the NCCs in the tissue of the senescent barley leaves. Oxidative loss of the formyl group from related linear tetrapyrroles has been noted (101). The original characterization for //v-NCC-1 (2) as a rusty pigment also pointed to the readiness of these reduced linear tetrapyrroles to undergo spontaneous reactions, which become manifest by the appearance of the rust colour (3, 4, 25). Clearly, these and other transformations, such as the one of //v-NCC-1 (2) to the two tetrapyrroles 31/epi-31, may reflect further degradation of the NCCs in the senescent tissue. 

P-450 arachidonic acid-derived metabolites have been identified in human urine [189]. The renal cytochrome P-450 system is involved in catalyzing the enzymatic transformation of arachidonic acid. This reaction can involve either an epoxygenase system yielding various epoxides or a mono oxygenase system yielding other oxidation products. Cells of the proximal tubule, thick ascending limb of Henle and the collecting duct contain the major amount of cytochrome P-450 enzyme in the kidney. 

The biosynthesis of these compounds seems to occur in two phases (1) coupling of two steroids via a pyrazine linker, and (2) relatively unselective oxidation at various positions. Some of these compounds are related to others by simple processes the hydration of cephalostatin 1 to its hemiketal form cephalostatin 9 the dehydration of cephalostatin 2 to an enone, which in turn may be an intermediate to cephalostatin 6 the skeletal rearrangement of ritterazine B to ritterazine A, which may be acid catalyzed and the pairs of ritterazines epimeric at C-22. One can speculate whether such reactions are non-enzymatic transformations occurring in the organism or even during the isolation procedure. 

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