title: Total synthesis, stereochemical assignment, and antimalarial activity of gallinamide A.
abstract: The total synthesis and stereochemical assignment of gallinamide A, an antimalarial depsipeptide of cyanobacterial origin, is described. Synthesis of the four possible N-terminal diastereoisomers of gallinamide A (including the natural product symplostatin 4) was achieved using a divergent strategy from a common imide fragment. The natural product and corresponding diastereoisomers were synthesized in 30-33% overall yield in a longest linear sequence of 8 steps. Comparative NMR spectroscopic studies of the four synthetic diastereoisomers with the isolated natural product demonstrated that gallinamide A possesses a dimethylated L-isoleucyl residue at the N-terminus. As such, we have shown that gallinamide A is structurally and stereochemically identical to symplostatin 4. Gallinamide A and its N-terminal diastereoisomers were also shown to possess significant antimalarial activity with IC(50) values in the nanomolar range against the 3D7 strain of Plasmodium falciparum.
authors: School of Chemistry, The University of Sydney, NSW 2006, Australia.
authors: Trent
authors: T
authors: Conroy
authors: Jin T
authors: JT
authors: Guo
authors: Roger G
authors: RG
authors: Linington
authors: Nicholas H
authors: NH
authors: Hunt
authors: Richard J
authors: RJ
authors: Payne
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D001688:Biological Products / Q000138:chemical synthesis*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000962:Antimalarials; D023181:Antimicrobial Cationic Peptides; D001688:Biological Products; D010455:Peptides; C534687:gallinamide A