Aminophosphonic Acids and Aminobis(phosphonic acids) as Potential Inhibitors of Penicillin‐Binding Proteins

Beck, Joséphine; Gharbi, Sonia; Herteg-Fernea, Adriana; Vercheval, Lionel; Bebrone, Carine; Lassaux, Patricia; Zervosen, Astrid; Marchand‐Brynaert, Jacqueline

doi:10.1002/ejoc.200800812

Cited by 25 publications

(17 citation statements)

References 79 publications

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“…Treatment of the imine derived from 4-aminobutanoic acid led to the formation of a mixture of -phosphoryl--amino acid ester and phosphorylated pyrrolidinone in 29% and 31% isolated yields, respectively (Scheme 17, A). 64 It is evident that the first step of the reaction is the hydrolysis of initial imine; it was found that the thus-formed amine cyclized spontaneously to furnish the target pyrrolidinone. The same approach was used to obtain a pseudopeptide-containing phosphorylated pyrrolidin-2-one moiety (Scheme 17, B).…”

Section: Scheme 16 Synthesis Of (R)-and (S)-phosphaprolines Via Intramentioning

confidence: 99%

Synthesis of Phosphaproline Derivatives: A Short Overview

et al. 2019

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Pyrrolidine-based phosphonates, analogues of the natural amino acid proline, possess a diverse set of biological activity. The goal of this short review is to summarize the major developments in the synthesis of phosphaproline derivatives reported since 2004 with special emphasis on the mechanisms and limitations of the methods presented.1 Introduction2 Phosphorylation of Pyrrolidine Derivatives2.1 Syntheses via Pudovik Reaction2.2 Syntheses via Arbuzov Reaction2.3 Decarboxylative Phosphorylation of Proline2.4 Direct C–H Bond Phosphorylation2.5 Other Reactions2.6 Overview of Phosphorylation Methods3 Synthesis of 2-Phosphorylpyrrolidines from Acyclic Precursors3.1 Cyclization of 4-Substituted Butylamine Derivatives3.2 [3+2]-Dipolar Cycloaddition of α-Iminophosphonates3.3 Cyclization of Aminoalkynes and 4-Aminocarbonyl Compounds4 Conclusions

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Section: Scheme 16 Synthesis Of (R)-and (S)-phosphaprolines Via Intramentioning

confidence: 99%

Synthesis of Phosphaproline Derivatives: A Short Overview

et al. 2019

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“…Classical ones include the formation of Schiff bases, which are then alkylated [150] or reduced [126], and synthesis of thioureido derivatives as intermediates in the preparation of heterocyclic compounds [151][152][153].…”

Section: Miscellaneousmentioning

confidence: 99%

Synthetic Procedures Leading towards Aminobisphosphonates

Chmielewska

Kafarski

2016

Molecules

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Abstract:Growing interest in the biological activity of aminobisphosphonates has stimulated the development of methods for their synthesis. Although several general procedures were previously elaborated to reach this goal, aminobisphosphonate chemistry is still developing quite substantially. Thus, innovative modifications of the existing commonly used reactions, as well as development of new procedures, are presented in this review, concentrating on recent achievements. Additionally, selected examples of aminobisphosphonate derivatization illustrate their usefulness for obtaining new diagnostic and therapeutic agents.

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“…Diisopropyl fluorophosphate (DIFP), which is efficient against serine proteases, was a poor inhibitor of E. coli PBP 5 (residual activity of 72% at a concentration of 1 mM after a pre-incubation of 1 h) [ 83 ]. A rather poor inhibition of Actinomadura R39 by phosphonic bioisoster of aminocitrate ( 22 , residual activity of 47% at a concentration of 500 µM) and pyrrolidinone ( 23 , residual activity of 67% at a concentration of 500 µM) ( Figure 9 ) was described [ 84 ]. The enzymatic assay with R39 was done using a thioester assay [ 53 ] and a pre- incubation time of one hour (it should be noted that the experimental details described in the original publication—fluorescent ampicillin and a 16 h pre-incubation—are not correct).…”

Section: Non-beta-lactamsmentioning

confidence: 99%

Development of New Drugs for an Old Target — The Penicillin Binding Proteins

et al. 2012

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The widespread use of β-lactam antibiotics has led to the worldwide appearance of drug-resistant strains. Bacteria have developed resistance to β-lactams by two main mechanisms: the production of β-lactamases, sometimes accompanied by a decrease of outer membrane permeability, and the production of low-affinity, drug resistant Penicillin Binding Proteins (PBPs). PBPs remain attractive targets for developing new antibiotic agents because they catalyse the last steps of the biosynthesis of peptidoglycan, which is unique to bacteria, and lies outside the cytoplasmic membrane. Here we summarize the “current state of the art” of non-β-lactam inhibitors of PBPs, which have being developed in an attempt to counter the emergence of β-lactam resistance. These molecules are not susceptible to hydrolysis by β-lactamases and thus present a real alternative to β-lactams. We present transition state analogs such as boronic acids, which can covalently bind to the active serine residue in the catalytic site. Molecules containing ring structures different from the β-lactam-ring like lactivicin are able to acylate the active serine residue. High throughput screening methods, in combination with virtual screening methods and structure based design, have allowed the development of new molecules. Some of these novel inhibitors are active against major pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and thus open avenues new for the discovery of novel antibiotics.

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Aminophosphonic Acids and Aminobis(phosphonic acids) as Potential Inhibitors of Penicillin‐Binding Proteins

Cited by 25 publications

References 79 publications

Synthesis of Phosphaproline Derivatives: A Short Overview

Synthesis of Phosphaproline Derivatives: A Short Overview

Synthetic Procedures Leading towards Aminobisphosphonates

Development of New Drugs for an Old Target — The Penicillin Binding Proteins

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