Bioactive Sulfonamides Derived from Amino Acids: Their Synthesis and Pharmacological Activities.

Abstract

Currently, the synthesis of bioactive sulfonamides using amino acid as a starting reagent has become an area of research interest in organic chemistry. Over the years, an amine-sulfonyl chloride reaction has been adopted as a common step in traditional sulfonamide synthetic methods. However, recent developments have shown amino acids to be better precursors than amines in the synthesis of sulfonamides. Although amines and amino acids have some structural similarities, using amino acids rather than amines in the synthesis of sulfonamides minimizes several drawbacks. Comparatively, amino acids are preferred to amines as starting reagents in sulfonamide synthesis due to their biological relevance, chirality, stereochemistry, diversity of side chains, orthogonality in functional group manipulation, the potential for peptide and protein synthesis, mild reaction conditions, alignment with green chemistry principles, diverse synthetic applications, easy availability, and economic viability. Amino acids, having the aforementioned properties, offer a versatile platform for the synthesis of sulfonamides with tailored structures. The reaction mechanism of the synthesis of amino acid-derived sulfonamides involves a nucleophilic attack by the amino group on the activated sulfonyl species to produce a sulfonamide functional group. Amino acid-based sulfonamides have numerous pharmacological activities, including antibacterial, antiviral, anticancer, antioxidant, anti-inflammatory, anti-plasmodial, antimalarial, anti-trypanosomal, and insect growth regulatory properties. This review discusses several synthetic processes, emphasizing established ways, cutting- edge techniques, and novel approaches that emphasize the significance of amino acids in the synthesis of sulfonamides. The structure-activity relationship of amino acid-derived sulfonamides and their pharmacological activities are also highlighted.