Stereochemical Assignment and Total Synthesis of An Antimalarial Lipopeptide

Abstract

Malaria is one of the prime causes that are responsible for the high mortality in this world. As more than 40% of the world?s population lives in malaria endemic areas, it is immediate need to discover cost effective drugs or vaccines for fighting against Plasmodium. falciparum. The lipopeptide (N1708) isolated from Streptomyces sp. exhibits promising activity against P. falciparum (IC50= 0.8 ?M against 3D7 strain). The natural product contains two non-proteinogenic amino acids (each having two stereogenic centers), aspartic acid and a long chain fatty acid (with one chiral centre and one double bond). In this work, we have hydrolysed the natural peptide and compared the natural fragments with that of synthetic amino acid steroisomers (prepared by asymmetric synthesis) using Marfey?s reagent derivatisation technique. This has allowed the configurational assignment of six unknown stereogenic centers. The full structure of N1708 has been confirmed by the total synthesis of the target lipopeptide.