Platensimycin

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Template:Chembox header| Platensimycin
Platensimycin
Chemical name 3-[[3-[(1R,3R,4R,5aR,9R,9aS)
-1,4,5,8,9,9a-hexahydro-3,9-dimethyl
-8-oxo-3H-1,4:3,5a-dimethano
-2-benzoxepin-9-yl]-1-oxopropyl]amino]
-2,4-dihydroxy-benzoic acid
Molecular formula C24H27NO7
Molar mass 441.18 g/mol

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Platensimycin is a member of a previously unknown class of antibiotics, which acts by blocking enzymes involved in the of the condensation steps in fatty acid biosynthesis,[1] which bacteria need to biosynthesise cell membranes (β-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/FabB). Other enzymes in this pathway have similarly been proven antibiotic targets for example FabI, the enoyl-ACP (acyl carrier protein) reductase, that is inhibited by isoniazid and related compounds and the antiseptic agent triclosan.[2] It is an experimental new drug in preclinical trials in an effort to combat MRSA in a mouse model.[3] The newly discovered natural product inhibitor was first isolated from a strain of Streptomyces platensis by the Merck group.[3]

Recently, a first total synthesis of racemic platensimycin has been published.[4] Its structure consists of a 3-amino-2,4-dihydroxybenzoic acid polar part linked through an amine bond to a lipophilic pentacyclicketolide.[4]

References

  1. Dieter Häbich, Franz von Nussbaum, ChemMedChem 2006, 1, 951–954. Platensimycin, a new antibiotic and "superbug challenger" from nature. PMID 16952137
  2. H T. Wright, and K.A Reynolds (2007) Antibacterial targets in fatty acid biosynthesis. Current Opinion in Microbiology doi:10.1016/j.mib.2007.07.001
  3. 3.0 3.1 Jun Wang et al, Platensimycin is a selective FabF inhibitor with potent antibiotic properties, Nature 441, 358-361 (18 May 2006) PMID 16710421
  4. 4.0 4.1 K. C. Nicolaou, A. Li, D. J. Edmonds, Angew. Chem. 2006, 118, 7244 – 7248; Angew. Chem. Int. Ed. 2006, 45, 7086 – 7090. PMID 17013803

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