Degradation rearrangement mechanisms

The API fenoprofen calcium is a diaryl ether. Degradation of fenopro-fen under intense ultraviolet light in solution yields a mixture of isomeric biphenyls via a photo-Fries rearrangement mechanism (Fig. 76) (117). 

The strongest support for the mechanism just outlined is the fact that many of the proposed intermediates have been isolated, and that these intermediates have been shown to yield the products of the Hofmann degradation. The mechanism is also supported by the fact that analogous mechanisms account satisfactorily for observations made on a large number of related rearrangements. Furthermore, the actual rearrangement step fits the broad pattern of 1,2-shifts to electron-deficient atoms. 

Refer to Figure 26.2 and propose a mechanism for the final step in the Edrnan degradation—the acid-catalyzed rearrangement of the ATZ derivative to the PTH derivative. 

Arene oxides can be intermediates in the bacterial transformation of aromatic compounds and initiate rearrangements (NIH shifts) (Dalton et al. 1981 Cerniglia et al. 1984 Adriaens 1994). The formation of arene oxides may plausibly provide one mechanism for the formation of nitro-substituted products during degradation of aromatic compounds when nitrate is present in the medium. This is discussed in Chapter 2. 

A rearrangement (NIH shift) occurred during the transformation of 2-chlorobiphenyl to 2-hydroxy-3-chlorobiphenyl by a methanotroph, and is consistent with the formation of an intermediate arene oxide (Adriaens 1994). The occurrence of such intermediates also offers plausible mechanisms for the formation of nitro-containing metabolites that have been observed in the degradation of 4-chlo-robiphenyl in the presence of nitrate (Sylvestre et al. 1982). 

In spite of its low vapor pressure, endrin has been found to volatilize significantly (20-30%) from soils within days after application (Nash 1983). In air, endrin will be primarily absorbed to particulates which may be re-entrained to soil or surface water via wet or dry deposition. Laboratory studies have indicated that a predominant mechanism for the transformation and degradation of endrin in air under field conditions is via photochemical reactions and rearrangements to yield primarily endrin ketone, with minor... 

Figure 11.3 Proposed PTT thermal degradation mechanism through the Mc-Clafferty rearrangement and the formation of acrolein and allyl alcohol...

Fig. 6.25. Simplified mechanism of two degradation reactions between peptides and reducing sugars occurring in solids, a) Maillard reaction between a side-chain amino (or amido) group showing the formation of an imine (Reaction a), followed by tautomerization to an enol (Reaction b) and ultimately to a ketone (Reaction c). Reaction c is known as the Amadori rearrangement (modified from [8]). b) Postulated mechanism of the reaction between a reducing sugar and a C-terminal serine. The postulated nucleophilic addition yields an hemiacetal (Reaction a) and is followed by cyclization (intramolecular condensation Reaction b). Two subsequent hydrolytic steps (Reactions c and d) yield a serine-sugar conjugate and the des-Ser-peptide...

Serajuddin et al. [19] reported that the degradation pathway of prevastatin sodium was directly linked to the micro-pH environment within the formulation. Under neutral conditions (pH 6.5), the statin formed two degradation products, a cyclic lactone and an internal hydroxyl rearrangement product. However, as the pH was increased to 9.9 with the incorporation of magnesium oxide into the blend, the only degradation mechanism involved the formation of the cleavage product, 2-methylpropanoic acid. This latter approach of increasing the... 

The mechanism of metabolic degradation of indol-3-ylacetic acid (39) is a matter of debate. A possible route demonstrated in vitro includes oxidative decarboxylation to skatolyl hydroperoxide (40), catalyzed by horseradish peroxidase isoenzyme C (HRP-C), followed by rearrangement to 3-(hydroxymethyl)oxindole (41), as shown in equation 12 . 

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