Synthesis of Cyclic Peptides as Potential Anti-Malarials

The results from the synthesis of peptides by Fmoc/SPPS on a 2-CTC resin and then lactamization in solution or solid phase for the preparation of cyclopeptides are presented. Both procedures allow the synthesis of the desired compounds in good to very good yield and with high cyclization efficiency for on-resin macrocyclization. In addition, the activities of the corresponding cyclopeptides against the chloroquine-resistant K1 strain of Plasmodium falciparum were evaluated. Cyclo-Cys(Trt)-Gly-Thr(tBu)-Gly-Cys(Trt)-Gly showed potent in vitro and selective activity against this parasite, EC50 = 28 nM.