Solution and solid phase peptide synthesis of macrocyclic analogues of natural products

During the past years our research group has been working on the development of synthetic methodologies to obtain cyclic peptides for their biological evaluation. Interesting results have been achieved for the evaluation of some of these compounds against Plasmodium falciparum K1 and Trypanosoma brucei brucei.1 These parasites are responsible for causing Malaria and African Trypanosomiasis respectively. Introduction of N-methylated amino acids in these cyclic peptides has proven to enhance their potency and selectivity. Versicotides A, B and C are cyclohexapeptide and cyclopentapeptides, produced by the marine fungus Aspergillus Versicolor ZLN-60.2 They present the unusual aminoacids N-methyl alanine and anthranilic acid in their structure. In this work, the solution approach to the synthesis of Versicotide C, as well as solid phase peptide synthesis (SPPS) of Versicotide’s A and B analogues will be presented. In these analogues, anthranilic acid is substituted by phenylalanine or tyrosine.