Biological aromatic hydroxylation

Replacement of the aromatic hydroxyl groups in isoproterenol by chlorine again causes a marked shift in biologic activity. 

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. 

Terrestrial and aquatic vascular plants promote the biological reduction of nitro groups on TNT to amine groups, yielding 2-ADNT and 4-ADNT, similar to invertebrates and vertebrates [13]. In vascular plants, the putative reduction enzyme is a nitroreductase [44], During reductive TNT biotransformation, ADNT products are accumulated within the plant tissue or excreted to the surrounding culture medium. For Myriophyllum species, the excreted ADNT products accounted for less than 20% of the initial TNT, and only trace levels of free ADNT remained in the biomass [37,38,42], One study [40] also showed that M. aquaticum was capable of oxidative transformation of TNT via methyl oxidation or aromatic hydroxylation, with oxidation products accounting for nearly 36% of the TNT initially added. 

Miyairi, S. and J. Fishman (1983). Novel method of evaluating biological 19-hydroxylation and aromatization of androgens. Biochem. Biophys. Res. Commun. 117, 392-398. 

There has been extensive work aimed at elucidating the mechanism of aromatic hydroxylation. Most of that research was carried out with the aim of modeling tyrosinase, a copper-containing monooxygenase, and other aromatic systems of biological relevance. This subject is discussed in connection with the hydroxylation of phenols. 

The naturally occurring catecholamines—dopamine (DA) (1), / -norepinephrine (/ -NE) (2), and / -epinephrine (/J-EPI) (3)— have many imiK)rtant biological functions. These catecholamines are produced in vivo from L-tyrosine. Tyrosine is first converted to dihydroxyphenylalanine (DOPA) by aromatic hydroxylation. L-DOPA is then decarboxylated to give DA, which is subsequently converted to / -NE by p-hydroxylation. DA is a vital neurotransmitter in the central nervous system (CNS) and has actions on the kidneys and heart. Norepinephrine is also present as a neurotransmitter in the CNS, and is the principal neurotransmitter of the peripheral sympathetic nervous system. Epinephrine, which is elaborated from / -NE by N-methylation in the adrenal medulla, has potent actions on the heart, smooth muscle, and other organs (/). 

Hydrazinopyridazines such as hydralazine have a venerable history as anti hypertensive agents. It is of note that this biological activity is maintained in the face of major modifications in the heterocyclic nucleus. The key intermediate keto ester in principle can be obtained by alkylation of the anion of pi peri done 44 with ethyl bromo-acetate. The cyclic acylhydrazone formed on reaction with hydrazine (46) is then oxidized to give the aromatized compound 47. The hydroxyl group is then transformed to chloro by treatment with phosphorus oxychloride (48). Displacement of halogen with hydrazine leads to the formation of endralazine (49). ... 

Direct hydroxylation of an aromatic ring to yield a hydroxybenzene (a phenol) is difficult and rarely done in the laboratory., but occurs much more frequently in biological pathways. An example is the hydroxylation of p-hydroxyphenyl acetate to give 3,4-dihydroxyphenyl acetate. The reaction is catalyzed by p-hydroxyphenylacctate-3-hydroxylase and requires molecular oxygen plus the coenzyme reduced flavin adenine dinucleotide, abbreviated FADH2. 

If an aromatic compound reacts with an OH radical to form a specific set of hydroxylated products that can be accurately identified and quantified in biological samples, and one or more of these products are not identical to naturally occurring hydroxylated species, i.e. not produced by normal metabolic processes, then the identification of these unnatural products can be used to monitor OH radical activity therein. This is likely to be the case if the aromatic detector molecule is present at the sites of OH radical generation at concentrations sufficient to compete with any other molecules that might scavenge OH radical. 

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