Abstract
Ortho-hydroxy-anilides are part of natural products like the new antibiotics platencin (A) and platensimycin (B). An important step in the total synthesis of these antibiotics or their derivatives is the preparation of the o-hydroxy-anilide partial structure. The presented method allows the preparation of o-hydroxy-anilides and o-dihydroxy-anilides from 2-nitrophenol esters in a one-step synthesis without protecting the hydroxy group. Aryl- and alkyl-anilides were prepared following this method as simple analogues of platensimycin (A). The resulting compounds were tested in an agar diffusion assay for their antibiotic potency.
Highlights
The 3-amino-2,4-dihydroxybenzoic acid core is an essential part of the new antibiotic drugs platencin (A) and platensimycin (B) [Figure 1], which show a high activity against Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE)
The following hydrogenation of the nitro group with Pd/C (5%) in methanol led to the amino group which reacted in the same procedure under aminolysis of the phenol ester to the resulting anilides 4a–g [14,15,16,17,18]
It is a helpful tool in preparing platensimycin analogues or other natural products containing this partial structure
Summary
The 3-amino-2,4-dihydroxybenzoic acid core is an essential part of the new antibiotic drugs platencin (A) and platensimycin (B) [Figure 1], which show a high activity against Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE). Platencin and platensimycin show a new mechanism of action by inhibiting the bacterial fatty acid synthesis. Bacterial fatty acid synthesis is carried out by fatty acid synthase (FAS II). Each step in this synthesis is encoded by separate proteins. A key step in the pathway is the condensation of the acyl-enzyme intermediate and malonyl-acyl carrier protein by catalysis of the FabF–enzyme towards the β-ketoacyl-acyl carrier protein (elongation of the fatty acid chain). Both natural products inhibit the FabF-enzyme (Fig. 2) [1,2,3,4]
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