Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 17, Issue 48, Pages 13544-13552Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201102538
Keywords
biological activity; malaria; natural products; parasiticides; peptides; total synthesis
Categories
Funding
- University of Sydney
- Australian Postgraduate Award
- National Health & Medical Research Council of Australia
Ask authors/readers for more resources
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 3033?% 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 IC50 values in the nanomolar range against the 3D7 strain of Plasmodium falciparum.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available