Platensimycin

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Platensimycin
IUPAC 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
Properties
Molecular formula C24H27NO7
Molar mass 441.47 g mol-1
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

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 Gram-positive bacteria need to biosynthesise cell membranes (β-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B)). 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] Platensimycin is a very effective antibiotic in vivo when continuously administered to cells, however this efficiency is reduced when administered by more conventional means.[4] The biosynthesis of plantensimycin has been studied using isotope incorporation experiments to show that the benzoic ring is produced from pyruvate and acetate via the TCA cycle, while the C-17 tetracyclic enone acid core is produced from the non-mevalonate terpenoid pathway.[4]

This natural product was first isolated from a strain of Streptomyces platensis by the Merck group.[3] A first total synthesis of racemic platensimycin has been published.[5] Its structure consists of a 3-amino-2,4-dihydroxybenzoic acid polar part linked through an amine bond to a lipophilic pentacyclicketolide.[5]

[edit] 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. ^ a b Jun Wang et al, Platensimycin is a selective FabF inhibitor with potent antibiotic properties, Nature 441, 358-361 (18 May 2006) PMID 16710421
  4. ^ a b K B. Herath, A B. Attygalle, and S B. Singh (2007) Biosynthetic Studies of Platensimycin. JACS Communications 11/23/2007 PMID 18034483
  5. ^ a b K. C. Nicolaou, A. Li, D. J. Edmonds, Angew. Chem. 2006, 118, 7244 – 7248; Angew. Chem. Int. Ed. 2006, 45, 7086 – 7090. PMID 17013803

[edit] External links


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