The pharmaceutical and biological importance of the amide moiety is briefly surveyed. Relationships between the electron density and chemical reactivity of the amide site are shortly described. Synthetic methods for the selective formation of monoaminodicarboxylic acid alpha and beta monoamides are summarised. The three major selective synthesis routes for the preparation of monoamides are introduced. The first class of synthetic methods consists of non selective formation of a- and b -esters, followed by their separation on the basis of different solubilities. Amidation of these esters results in the α- or β-amides respectively. The second class of the reactions utilises the orientating capacity of the amino (ammonium) site, producing first various cyclic anhydrides, lactames, lactones, which are then decomposed in hydrolytic, aminolytic, etc. reactions, resulting selectively in the α- or β-amides or esters. Reactants in the third class of the reactions are dicarboxylic acids with carbon-carbon π-bonds, and ammonia (or alkyl-amine) which form the appropriate compound in addition reactions. Reactivities and selectivities are interpreted in terms of inductive effects, acidity differences and electronic effects of the various protecting groups. Some important analytical properties of monoamino-dicarboxylic acids and their monoamides are compiled.
|Number of pages||9|
|Journal||Acta pharmaceutica Hungarica|
|Publication status||Published - May 6 2003|
ASJC Scopus subject areas
- Pharmaceutical Science