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

Shibaji K Ghosh; Brinda Somanadhan; Kevin S-W Tan; Mark S Butler; Martin J Lear

doi:10.1021/ol300293a

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.

Authors

Shibaji K Ghosh¹, Brinda Somanadhan, Kevin S-W Tan, Mark S Butler, Martin J Lear

Affiliation

¹ 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.

PMID: 22390733
DOI: 10.1021/ol300293a

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