ChloroquineV1, Main, Exploration, bibRecord, 001494

Total Synthesis, Stereochemical Assignment, and Antimalarial Activity of Gallinamide A

Identifieur interne : 001494 ( Main/Exploration ); précédent : 001493; suivant : 001495

Total Synthesis, Stereochemical Assignment, and Antimalarial Activity of Gallinamide A

Auteurs : Trent Conroy [Australie] ; Jin T. Guo [Australie] ; Roger G. Linington [États-Unis] ; Nicholas H. Hunt [Australie] ; Richard J. Payne [Australie]

Source :

Chemistry – A European Journal [ 0947-6539 ] ; 2011-11-25.

RBID : ISTEX:EA4F2BC5DE52CE319CF3459C9C894C15A72A5A43

English descriptors

Teeft :
- Amino, Amino ester, Antimalarial, Calcd, Cdcl3, Chcl3, Chem, Column chromatography, Deprotected, Diastereoisomers, Eluent, Ester, Et3n, Falciparum, Fmoc, Fmoc deprotected, Free base, Gallinamide, General procedure, Gmbh, Hplc, Hrms, Imide, Kgaa, Mecn, Meoh, Mmol, Moiety, Natural product, Natural products, Phase hplc, Possible diastereoisomers, Pyrrolinone, Quant, Room temperature, Symplostatin, Thin film, Total synthesis, Trifluoroacetate, Trifluoroacetate salt, Trifluoroacetate salts, Vacuo, Verlag, Verlag gmbh, Weinheim, Weinheim chem.

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 IC50 values in the nanomolar range against the 3D7 strain of Plasmodium falciparum.

Naturally active: The total synthesis of gallinamide A, a cyanobacterium‐derived depsipeptide, is described. Four N‐terminal diastereoisomers of gallinamide A were prepared by using two key fragments (see scheme). Spectroscopic comparison to the isolated natural product enabled the absolute configuration of the N,N‐dimethylated isoleucyl residue to be determined as 25S, 26S. Gallinamide A (and its diastereoisomers) were also shown to possess potent antimalarial activity.

Url:

https://api.istex.fr/ark:/67375/WNG-QXPV063J-D/fulltext.pdf

DOI: 10.1002/chem.201102538

Affiliations:

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Le document en format XML

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<term>Cdcl3</term>
<term>Chcl3</term>
<term>Chem</term>
<term>Column chromatography</term>
<term>Deprotected</term>
<term>Diastereoisomers</term>
<term>Eluent</term>
<term>Ester</term>
<term>Et3n</term>
<term>Falciparum</term>
<term>Fmoc</term>
<term>Fmoc deprotected</term>
<term>Free base</term>
<term>Gallinamide</term>
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<term>Hplc</term>
<term>Hrms</term>
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<term>Kgaa</term>
<term>Mecn</term>
<term>Meoh</term>
<term>Mmol</term>
<term>Moiety</term>
<term>Natural product</term>
<term>Natural products</term>
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<term>Possible diastereoisomers</term>
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<term>Thin film</term>
<term>Total synthesis</term>
<term>Trifluoroacetate</term>
<term>Trifluoroacetate salt</term>
<term>Trifluoroacetate salts</term>
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<front><div type="abstract" xml:lang="en">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 IC50 values in the nanomolar range against the 3D7 strain of Plasmodium falciparum.</div>
<div type="abstract" xml:lang="en">Naturally active: The total synthesis of gallinamide A, a cyanobacterium‐derived depsipeptide, is described. Four N‐terminal diastereoisomers of gallinamide A were prepared by using two key fragments (see scheme). Spectroscopic comparison to the isolated natural product enabled the absolute configuration of the N,N‐dimethylated isoleucyl residue to be determined as 25S, 26S. Gallinamide A (and its diastereoisomers) were also shown to possess potent antimalarial activity.</div>
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Total Synthesis, Stereochemical Assignment, and Antimalarial Activity of Gallinamide A

Total Synthesis, Stereochemical Assignment, and Antimalarial Activity of Gallinamide A

Source :

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri