5.4 : Phase I Reactions: Oxidation of Carbon-Heteroatom and Miscellaneous Systems

Oxidative reactions are pivotal in metabolizing numerous compounds, including pharmaceutical drugs. These reactions often occur in carbon-heteroatom systems, such as carbon-nitrogen, carbon-sulfur, and carbon-oxygen.

In carbon-nitrogen systems, aliphatic and aromatic amines can undergo oxidative reactions. Secondary and tertiary amines, like those found in tricyclic antidepressants, can undergo N-dealkylation, a process that involves the oxidation of the alkyl group. In addition, oxidative deamination can occur, resulting in the formation of simpler amines, such as amphetamine.

Additional transformations can also occur, such as N-oxide formation in basic nitrogen atoms and N-hydroxylation in non-basic nitrogen atoms or those lacking an α-hydrogen.

Carbon-sulfur systems can undergo processes like S-dealkylation, S-alkylation, desulphurization, and S-oxidation. Sulphonamides and thiols, commonly found in various drugs, typically undergo these reactions. In contrast, carbon-oxygen systems predominantly undergo O-dealkylation. A classic example of a drug undergoing this type of reaction is codeine.

In addition to these specific reactions, there are also miscellaneous oxidative reactions. For example, reductive dehalogenation can occur in fluorocarbons like halothane, and the reduction of sulfur-containing groups can be seen in drugs like disulfiram. Understanding these complex biochemical reactions is critical in the pharmaceutical industry. Researchers and healthcare professionals can design and administer safer and more effective therapies by understanding how different compounds interact with the body's metabolic processes.