Synthesis, Conformational Studies and Biological Profiles of Tetrahydrofuran Amino‐Acid‐Containing Cationic Antitubercular Peptides

Linear cationic tetra‐ and octapeptides containing a tetrahydrofuran amino acid were synthesised, a conformational analysis performed, and their structure–activity relationships explored by evaluating their antibacterial, antitubercular and cytotoxic properties. Only the octapeptides showed activities, which was weak to moderate against Gram‐positive and Gram‐negative bacteria for only two peptides, but was very significant against Mycobacterium tuberculosis, and peptides were devoid of toxicity towards mammalian Vero cells. N‐Terminus‐deprotected esters showed the best results with excellent selectivity for M. tuberculosis and these peptides promise to be potential leads. Ring the changes: A tetrahydrofuran‐based amino acid was incorporated into linear tetrapeptide and octapeptide analogues of gramicidin S. An NMR study on the conformations of these peptides, along with their biological activities against a panel of bacteria, in particular Mycobacterium tuberculosis, and a mammalian cell line, is reported.