Absolute configuration and total synthesis of a novel antimalarial lipopeptide by the de novo preparation of chiral nonproteinogenic amino acids

Org Lett. 2012 Mar 16;14(6):1560-3. doi: 10.1021/ol300293a. Epub 2012 Mar 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Catalysis
  • Fatty Acids / chemistry
  • HeLa Cells
  • Humans
  • Lipopeptides / chemical synthesis*
  • Lipopeptides / chemistry
  • Lipopeptides / pharmacology
  • Molecular Structure
  • Plasmodium falciparum / drug effects*
  • Stereoisomerism
  • Streptomyces / chemistry*

Substances

  • Amino Acids
  • Antimalarials
  • Fatty Acids
  • Lipopeptides