p -Toluenesulfonyl Chloride Catalysed Facile Synthesis of O -benzyl- l -amino Acids and Their In Vitro Evaluation

Protection and subsequent deprotection of amino acid functional groups play a key role in regioselective peptide synthesis. For protection, carboxylic acid functional groups are often benzylated using p-toluenesulfonic acid catalysed Fischer-Speier esterification reaction. Such reaction involves in situ water formation, which requires subsequent separation by azeotropic distillation for forward shift of equilibrium. To eliminate the need of this corresponding step requiring additional set-up, current study investigated p-toluenesulfonyl chloride as a reasonable alternative catalyst for facile benzylation of selected mono- and di- carboxylic amino acids. Literature reports that p-toluenesulfonyl chloride not only has a better shelf life but also demonstrates better safety in case of accidental systemic absorption over p-toluenesulfonic acid. As the O-benzyl-l-amino acids are often retained without deprotection to constitute the pharmaceutical peptide systems, synthesized compounds were investigated for their biocompatibility using in vitro cytotoxicity assays.