Aromatic rings enzymatic hydroxylation

An alternative to the enzymatic /V-hydroxylation, the first stage in carcinogenesis, is C-hydroxylation in the aromatic ring. This is an important mode of detoxification. 

NIH shift The INTRAMOLECULAR hydrogen MIGRATION that can be observed in enzymatic and chemical hydroxylations of aromatic rings. It is evidenced by appropriate deuterium labeling, for example ... 

Capsaicin and capsaicinoids undergo Phase I metabolic conversion involving both oxidative and non-oxidative paths. The liver is the major site of this enzymatic activity. Lee and Kumar (1980) demonstrated the conversion of catechol metabolites via hydroxylation of vanil-lyl ring. In rats, dihydrocapsaicin is metabolized to products that are excreted in the urine as glu-curonides (Kawada and Iwai, 1985). The generation of a quinone derivative occurs via O-demethylation at the aromatic ring with concomitant oxidation of the semiquinone and quinone derivatives or via demethylation of the phenoxy radical intermediate of capsaicin. Additionally, the alkyl side chain of capsaicin is also susceptible to oxidative deamination (Wehmeyer et al., 1990). There is evidence that capsaicinoids can undergo aliphatic oxidation (cu-oxidation) (Surh et al, 1995 Reilly et al, 2003) which is a possible detoxification pathway. Non-oxidative pathways are also involved in the bioconversion of capsaicin, e.g. hydrolysis of the acid-amide bond to yield vanillylamine and fatty acyl moieties (Kawada et al, 1984 Kawada and Iwai, 1985 Oi et al, 1992). 

In the previous chapter Synthesis of Phenol Polymers Using Peroxidases , the enzymatic oxidative polymerization of monophenolic derivatives is described. This chapter deals with the enzymatic synthesis and properties of polymers from polyphenols, compounds having more than two hydroxyl groups on the aromatic ring(s). In particular, cured phenolic polymers (artificial urushi) and flavonoid polymers are examined from the standpoint of the enzymatic synthesis of functional materials. 

MSA does not contain any chiral carbon centers. Before the aromatization of the six-membered ring occurs, two prochiral carbons (C-2 and C-4 in the six-carbon intermediate) evolve, each of which loses a hydrogen in the process of the dehydratization/aromatization steps. In addition, C-3 of the six-carbon intermediate forms a chiral center when the ketone is reduced to a hydroxyl by a ketoreductase activity (Fig. 5). The chirality of this hydroxyl carbon is unclear since the intermediate has not been isolated. It is also unknown if this carbon retains its chirality in an eight-carbon intermediate or whether the hydroxyl is eliminated by dehydration prior to the third condensation reaction. The stereospecificity at the prochiral C-2 and C-4 carbons in the reaction intermediates was addressed using chemically synthesized (] )- and (S)-[1- C, 2- H]malonate precursors which were enzymatically converted into CoA derivatives via succinyl CoA transferase [127,128]. Thus, the prochiral methylene in malonyl CoA was replaced by chiral, double-labeled (S)- or (J )-[1- C, 2- H]malonyl CoA substrates in the reaction mixture with 6-MSAS. The condensation is expected to occur with inversion of configuration and the intact methylene... 

Evidence for the direct oxidation of benzene (or substituted benzenes) to benzene oxide (or substituted benzene oxides) by enzymatic (Refs. 5 and 35 and references therein) and chemical (Refs, 35 and 36 and references therein) methods is available both from the observation of the migration and retention of ring substituents during aromatic hydroxylation (NIH shift),and from the nature of the isolated products (phenols, rans-dihydrodiols). As a direct consequence of its thermal instability and high reactivity, benzene oxide 1 has not yet been isolated as an oxidation product of benzene. 

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