Total synthesis, stereochemical assignment, and antimalarial activity of gallinamide A |
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Authors: | Conroy Trent Guo Jin T Linington Roger G Hunt Nicholas H Payne Richard J |
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Institution: | School of Chemistry, The University of Sydney, NSW 2006, Australia. |
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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. |
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Keywords: | biological activity malaria natural products parasiticides peptides total synthesis |
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