With the total synthesis of plusbacin A3 complete, ..

Both katanosin B and plusbacin A3 are naturally occurring cyclic depsipeptide antibiotics containing a lactone linkage. They showed strong antibacterial activity against methicillin-resistant Staphylococcus aureus and VanA-type vancomycin-resistant enterococci, with MICs ranging from 0.39 to 3.13 μg/ml, as well as against other gram-positive bacteria. They inhibited the incorporation of N-acetylglucosamine, a precursor of cell wall synthesis, into peptidoglycan of S. aureus whole cells at concentrations close to their MICs. In vitro studies with a wall-membrane particulate fraction of S. aureus showed that katanosin B and plusbacin A3 inhibited the formation of lipid intermediates, with 50% inhibitory concentrations (IC50s) of 2.2 and 2.3 μg/ml, respectively, and inhibited the formation of nascent peptidoglycan, with IC50s of 0.8 and 0.4 μg/ml, respectively. Vancomycin, a well-known inhibitor of transglycosylation, did not inhibit the formation of lipid intermediates but did inhibit the formation of nascent peptidoglycan, with an IC50 of 4.1 μg/ml. Acetyl-Lys--Ala--Ala, an analog of the terminus of the lipid intermediates, effectively suppressed the inhibition of transglycosylation by vancomycin, but did not suppress those by katanosin B and plusbacin A3. These results indicate that the antibacterial activity of katanosin B and plusbacin A3 is due to blocking of transglycosylation and its foregoing steps of cell wall peptidoglycan synthesis via a mechanism differing from that of vancomycin.

Total synthesis of plusbacin A3: a depsipeptide …
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Direct asymmetric aldol reaction, catalyzed by both metallic complexes and purely organic molecules now becomes one of the most desired tools in organic chemistry. After an initial period of validating methodology by using a wide range of important model reactions, the time has now been reached to address specific synthesis and solve pending problems of practical relevance. In this review we describe recently discovered, most important and most flexible catalysts for direct asymmetric aldol reaction and their application in total synthesis of target natural products and known compounds of biological and pharmaceutical relevance.


Total synthesis and antibacterial investigation of plusbacin A3

effects on peptidoglycan and wall teichoic acid biosyntheses in Staphylococcus aureus.
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The total synthesis of plusbacin A3 (1) has been accomplished using a solvent-dependent diastereodivergent Joullié–Ugi three-component reaction (JU-3CR) as a key step. Two -3-hydroxy--proline residues were constructed by combining the JU-3CR with a convertible isocyanide strategy. Subsequent peptide coupling and macrolactamization afforded plusbacin A3. Investigating the antibacterial activity of 1 compared with that of its dideoxy analogue revealed that the -β-hydroxyaspartic acid residues are essential for antibacterial activity. Notably, there is a low potential for the development of resistance in . against plusbacin A3.


KATSUYAMA AKIRA - Researcher - researchmap

The total synthesis of plusbacin A3 (1) has been accomplished using a solvent-dependent diastereodivergent Joullié–Ugi three-component reaction (JU-3CR) as a key step. Two -3-hydroxy--proline residues were constructed by combining the JU-3CR with a convertible isocyanide strategy. Subsequent peptide coupling and macrolactamization afforded plusbacin A3. Investigating the antibacterial activity of 1 compared with that of its dideoxy analogue revealed that the -β-hydroxyaspartic acid residues are essential for antibacterial activity. Notably, there is a low potential for the development of resistance in . against plusbacin A3.