Aromatic compound biological hydroxylation

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 with ethyl bromo-acetate. The cyclic acylhydrazone formed on reaction with hydrazine (46) is then oxidized to give the aromatized compound The hydroxyl group is then transformed to... 

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. 

A particular type of hydroxylation of aromatic compounds is the hydroxylation of indoles (XIII), which yield biologically active oxindoles (XIV) in nearly quantitative yields (Scheme VIII) [79],... 

Such cyclic peroxides have been proposed as intermediates in photochemical and chemiluminescent reactions of aromatic compounds with oxygen (4, 5, 44) and in the biological hydroxylation of aromatic compounds (22, 23, 34). In dilute ferrous ion solution the cyclic peroxides could decompose ionically to give a predominantly electrophilic distribution of substituted phenols, while at higher concentrations the ferrous ion would cleave the peroxide bond homolytically this, followed by loss of water, would give a more random pattern of substituted phenols. 

The chemistry of aromatic compounds is dominated hy electrophilic aromatic substitution reactions, both in the laboratory and in biological pathways. Many variations of the reaction can be carried out, including halogenation, nitration, sulfonation, and hydroxylation. Friedel-Crafts alkylation and acylation, which involve reaction of an aromatic ring with carho-cation electrophiles, are particularly useful. 

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