Total Synthesis and Biological Investigation of (−)-Promysalin

Steele, A. Duncan; Knouse, Kyle W.; Keohane, Colleen E.; Wuest, William M.

doi:10.1021/jacs.5b04767

Cited by 36 publications

(59 citation statements)

References 27 publications

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“…281 Genomic analysis of the biosynthetic cluster proposed by De Mot indicated that the natural L-proline is incorporated into the natural product; the remaining stereocenters were both in the myristate side chain. This synthetic approach featured a convergent strategy in which precursors each containing one stereocenter were joined through cross-metathesis, permitting straightforward preparation of the various diastereomers.…”

Section: Narrow-spectrum Small Molecule Natural Productsmentioning

confidence: 99%

Natural Products as Platforms To Overcome Antibiotic Resistance

2017

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Natural products have served as powerful therapeutics against pathogenic bacteria since the golden age of antibiotics of the mid-20th century. However, the increasing frequency of antibiotic-resistant infections clearly demonstrates that new antibiotics are critical for modern medicine. Because combinatorial approaches have not yielded effective drugs, we propose that the development of new antibiotics around proven natural scaffolds is the best short-term solution to the rising crisis of antibiotic resistance. We analyze herein synthetic approaches aiming to reengineer natural products into potent antibiotics. Furthermore, we discuss approaches in modulating quorum sensing and biofilm formation as a nonlethal method, as well as narrowspectrum pathogen-specific antibiotics, which are of interest given new insights into the implications of disrupting the microbiome.

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Section: Narrow-spectrum Small Molecule Natural Productsmentioning

confidence: 99%

Natural Products as Platforms To Overcome Antibiotic Resistance

2017

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“…Moreover,i ta lso kills persister cells effectively without showing toxicity to mammalian cells. [254] Moreover, these compounds do not cause damage to human cells.…”

Section: Biofilm Inhibitorsmentioning

confidence: 99%

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

et al. 2018

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The public view on antibiotics as reliable medicines changed when reports about "resistant superbugs" appeared in the news. While reasons for this resistance development are easily spotted, solutions for re-establishing effective antibiotics are still in their infancy. This Review encompasses several aspects of the antibiotic development pipeline from very early strategies to mature drugs. An interdisciplinary overview is given of methods suitable for mining novel antibiotics and strategies discussed to unravel their modes of action. Select examples of antibiotics recently identified by using these platforms not only illustrate the efficiency of these measures, but also highlight promising clinical candidates with therapeutic potential. Furthermore, the concept of molecules that disarm pathogens by addressing gatekeepers of virulence will be covered. The Review concludes with an evaluation of antibacterials currently in clinical development. Overall, this Review aims to connect select innovative antimicrobial approaches to stimulate interdisciplinary partnerships between chemists from academia and industry.

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“…Kürzlich wurden kationische Pillararene (Abbildung 17) als Biofilm-Inhibitoren nachgewiesen, welche die Bildung des Biofilms bei sub-MIC-Konzentrationen in verschiedenen, klinisch relevanten Gram-positiven Pathogenen, einschließlich S. aureus und E. faecalis verhindern. [254] [249] Zusätzlich zu synthetischen Molekülen gibt es in der Natur eine Vielzahl an niedermolekularen Substanzen, die auf die Bekämpfung der Biofilm-Bildung zugeschnitten sind.…”

Section: Angewandte Chemieunclassified

Über bisherige Denkweisen hinaus – neue Wirkstoffe zur Überwindung der Antibiotika‐Krise

et al. 2018

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Die öffentliche Wahrnehmung von Antibiotika als verlässliche Arzneimittel veränderte sich drastisch, als Meldungen über “multiresistente Super‐Erreger” die Nachrichten aufrüttelten. Während die Ursachen für die bakterielle Resistenzentwicklung schnell erkannt wurden, befindet sich die Forschung zur Wiedergewinnung von Antibiotika als effektive Arzneistoffe immer noch am Anfang. Dieser Aufsatz umfasst zahlreiche Aspekte des Entwicklungsprozesses neuer Antibiotika, von der Grundlagenforschung bis zum fertigen Medikament. Er bietet einen interdisziplinären Überblick über Methoden zur Identifizierung neuer Antibiotika und erörtert Strategien, um ihren molekularen Wirkmechanismus aufzuklären. Die Darstellung ausgewählter Antibiotika, die kürzlich mithilfe dieser Plattformen entdeckt wurden, verdeutlicht die Effizienz der Ansätze und hebt vielversprechende klinische Kandidaten mit therapeutischem Potential hervor. Zusätzlich wird das Konzept von Molekülen erörtert, die Krankheitserreger “entwaffnen”, indem sie Schlüsselpunkte der Virulenz adressieren. Der Aufsatz schließt mit einer kritischen Beurteilung jener antibakteriellen Wirkstoffe, die sich derzeit in klinischer Entwicklung befinden. Insgesamt soll dieser Aufsatz ausgewählte, innovative antibakterielle Ansätze verknüpfen, um interdisziplinäre Partnerschaften zwischen Chemikern aus der akademischen und industriellen Forschung anzuregen.

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Total Synthesis and Biological Investigation of (−)-Promysalin

Cited by 36 publications

References 27 publications

Natural Products as Platforms To Overcome Antibiotic Resistance

Natural Products as Platforms To Overcome Antibiotic Resistance

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

Über bisherige Denkweisen hinaus – neue Wirkstoffe zur Überwindung der Antibiotika‐Krise

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