ABSTRACT
The first pyridine-based natural compound to come to the fore was niacin. This chapter provides a general overview of the synthesis of pyridine derivatives by multicomponent reactions, with emphasis on those methods that have been found to be particularly suitable for the preparation of bioactive compounds. These reactions will be presented taking into account the type of disconnection that they involve. [2+2+1+1] approach is one of the most common methods for the construction of the pyridine nucleus: the Hantzsch reaction, which was one of the first multicomponent reactions to be described in the literature. Some variations to the original [2+2+1+1] Hantzsch pyridine synthesis based on the use of substrates bearing at least one nitrile functionality to replace one or both of ß-dicarbonyl compounds have been described. The most efficient method to synthesize nonsymmetrical Hantzsch pyridines is to employ the modified three-component Hantzsch approach, leading to the pyridine ring via a [3+2+1] disconnection.
