NIH shifts

Transition-metal complexes such as [Rh(CO)2Cl]2,204 Rh(butadiene)2Cl,205 or Cr(CO)3(NH3)312 have also been used for the deoxygenation of oxepins to give 312,204 205 and benzoxepins to give 4.12,204 Occasionally, substantial amounts of phenolic compounds have been isolated due to the competing NIH shift of the arene oxide.204 1-Benzoxepin and 3-benzoxepin resist oxygen extrusion under these conditions probably due to their inability to form arene oxi-des.133,204... 

Figure 11.16 Proposed NIH shift mechanism for hydroxyla-tion of the azinomycin naphthoate.

In addition to nonheme iron complexes also heme systems are able to catalyze the oxidation of benzene. For example, porphyrin-like phthalocyanine structures were employed to benzene oxidation (see also alkane hydroxylation) [129], Mechanistic investigations of this t3 pe of reactions were carried out amongst others by Nam and coworkers resulting in similar conclusions like in the nonheme case [130], More recently, Sorokin reported a remarkable biological aromatic oxidation, which occurred via formation of benzene oxide and involves an NIH shift. Here, phenol is obtained with a TON of 11 at r.t. with 0.24 mol% of the catalyst. 

Some green algae are able to use aromatic sulfonic acids (Figure 2.4a) (Soeder et al. 1987) and aliphatic sulfonic acids (Figure 2.4b) (Biedlingmeier and Schmidt 1983) as sources of sulfur. Cultures of Scenedesmus obliquus under conditions of sulfate limitation metabolized naphthalene-l-sulfonate to l-hydroxy-naphthalene-2-sulfonate and the gluco-side of naphth-l-ol (Kneifel et al. 1997). These results are consistent with formation of a 1,2-epoxide followed by an NIH shift. 

Fungal and yeast biotransformations of PAHs production of phenols by NIH shift... 

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. 

Cerniglia CE, JP Ereeman, EE Evans (1984) Evidence for an arene oxide-NIH shift pathway in the transformation of naphthalene to 1-naphthol hy Bacillus cereus. Arch Microbiol. 138 283-286. 

Eairley DJ, DR Boyd, ND Sharma, CCR Allen, P Morgan, MJ Larkin (2002) Aerobic metabolism of 4-hydroxybenzoic acid in Archaea via an unusual pathway involving an intramolecular migration (NIH shift). Appl Environ Microbiol 68 6246-6255. 

Narro ML, CE Cerniglia, C Van Baalen, DT Gibson (1992) Evidence for an NIH shift in oxidation of naphthalene by the marine cyanobacterium Oscillatoria sp. strain JCM. Appl Environ Microbiol 58 1360-1363. 

Cerniglia CE, JR Althus, EE Evans, JP Freeman, RK Mitchum, SK Yang (1983) Stereochemistry and evidence for an arene oxide-NIH shift pathway in the fungal metabolism of naphthalene. Chem-Biol Interactions 44 119-132. 

Daly JW, DM Jerina, B Witkop (1972) Arene oxides and the NIH shift the metabolism, toxicity and carcinogenicity of aromatic compounds. Experientia 28 1129-1149. 

Unusual pathways have been found in the bacterial degradation of a number of 4-hydroxybenzoates and related compounds, and in some of them rearrangements (NIH shifts) are involved ... 

Gentisate is formed by a strain of Bacillus sp. in an unusual rearrangement from 4-hydroxybenzoate (Crawford 1976) that is formally analogous to the formation of 2,5-dihydroxyphenylacetate from 4-hydroxyphenylacetate by Pseudomonas acidovorans (Hareland et al. 1975). Similarly, the metabolism of 4-hydroxybenzoate by the archaeon Haloarcula sp. strain D1 involves the formation of 2,5-dihydroxybenzoate (Fairley et al. 2002). All these reactions putatively involve an NIH shift. 

Pseudomonas sp. strain P.J. 874 grown with tyrosine carried out dioxygenation of 4-hydroxyphenylpyruvate to 2,5-dihydroxyphenylacetate accompanied by an NIH shift (Lindstedt et al. 1977). The involvement of a high-spin ferric center coordinated with tyrosine is conclusively revealed in the primary structure of the enzyme (Riietschi et al. 1992). 

Hartmann S, C Hultschig, W Eisenreich, G Fuchs, A Bacher, S Ghisla (1999) NIH shift in flavin-dependent monooxygenation mechanistic studies with 2-aminobenzoyl-CoA monooxygenase/reductase. Proc Natl Acad USA 96 7831-7836. 

Mutations at the active site of CYPlOl (cytochrome P450j,j jj) from a strain of Pseudomonas putida made possible the monooxygenation of chlorinated benzenes with less than three substituents to chlorophenols, with concomitant NIH shifts for 1,3-dichlorobenzene (Jones et al. 2001). Further mutations made it possible to oxidize even pentachlorobenzene and hexachlorobenzene to pentachlorophenol (Chen et al. 2002). Integration of the genes encoding cytochrome PTSO. into Sphingobium chlorophenolicum enabled this strain to partially transform hexachlorobenzene to pentachlorophenol (Yan et al. 2006). 

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). 

The NIH shift (Daly et al. 1972) with translocation of chlorine has been demonstrated during the biotransformation of 2,4-dichlorophenoxyacetate by Aspergillus niger (Figure 9.24) (Faulkner and Woodcock 1965). The NIH shift is not restricted to fungi since it has also been demonstrated with protons—though less frequently with other substituents—in prokaryotes. 

FIGURE 9.24 NIH shift during the metabolism of 2,4-dichlorophenoxyacetate hy Aspergillus niger. 

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