Absolute Configuration and Total Synthesis of a Novel Antimalarial Lipopeptide by the de Novo Preparation of Chiral Nonproteinogenic Amino Acids

Abstract

The absolute configuration (via degradation and Marfey's derivatization studies) and the total synthesis of a novel antimalarial lipid-peptide isolated from Streptomyces sp. (IC(50) = 0.8 μM, Plasmodium falciparum 3D7) is disclosed. To this end, versatile stereocontrolled routes to nonproteinogenic amino acids (via catalytic Mannich, Sharpless methods) and enantiomeric trans fatty acids (via Evans alkylation, Kocienski-Julia olefination) have been developed.