title: 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.
authors.affiliation: Department of Chemistry, Faculty of Science, and Medicinal Chemistry Program of the Life Sciences Institute, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
authors.forename: Shibaji K
authors.initials: SK
authors.lastname: Ghosh
authors.forename: Brinda
authors.initials: B
authors.lastname: Somanadhan
authors.forename: Kevin S-W
authors.initials: KS
authors.lastname: Tan
authors.forename: Mark S
authors.initials: MS
authors.lastname: Butler
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lear
mesh_terms: D000478:Alkylation; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D005227:Fatty Acids / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D055666:Lipopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D000962:Antimalarials; D005227:Fatty Acids; D055666:Lipopeptides