Practical Synthesis of the New Carbapenem Antibiotic Ertapenem Sodium

Williams, J. M.; Brands, Karel M. J.; Skerlj, Renato T.; Jobson, Ronald B.; Marchesini, G.; Conrad, Kendon J.; Pipik, Brenda; Savary, Kimberly; Tsay, Fuh‐Rong; Houghton, Peter G.; Sidler, Daniel R.; Dolling, Ulf H.; DiMichele, Lisa; Novak, Thomas J.

doi:10.1021/jo0501442

Cited by 29 publications

(13 citation statements)

References 37 publications

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“…As expected, MALDI-TOF MS of ertapenem showed four peaks: 450 Da (hydrolyzed and decarboxylated ertapenem without sodium), 476 Da (ertapenem without sodium), 498 Da (monosodium salt), and 521 Da (disodium salt) (15). Subsequently, we conducted kinetic studies with strains known to carry carbapenemases (Table 1).…”

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confidence: 59%

Using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry To Detect Carbapenem Resistance within 1 to 2.5 Hours

2011

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In recent years, the percentage of carbapenem-resistant bacteria has increased at an alarming pace and become a major threat for patient survival. Carbapenemase-induced carbapenem resistance can be confirmed through the detection of carbapenem degradation using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). This method works for strains carrying NDM-1, VIM-1, VIM-2, KPC-2, and different IMP enzymes.

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confidence: 59%

Using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry To Detect Carbapenem Resistance within 1 to 2.5 Hours

2011

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“…[113] Further improvements were subsequently made (frequent dosing is still required with meropenem), leading to the 2001 approval of another fully synthetic C1-bmethyl carbapenem, ertapenem (Merck). [114] Carbapenems are not the only fully synthetic b-lactams that have become important antibiotics. In 1981, two research groups independently reported the isolation of monocyclic blactam ("monobactam") natural products from different bacterial strains.…”

Section: Antibacterial Drug Discoverymentioning

confidence: 99%

The Evolving Role of Chemical Synthesis in Antibacterial Drug Discovery

2014

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The discovery and implementation of antibiotics in the early twentieth century transformed human health and wellbeing. Chemical synthesis enabled the development of the first antibacterial substances, organoarsenicals and sulfa drugs, but these were soon outshone by a host of more powerful and vastly more complex antibiotics from nature: penicillin, streptomycin, tetracycline, and erythromycin, among others. These primary defences are now significantly less effective as an unavoidable consequence of rapid evolution of resistance within pathogenic bacteria, made worse by widespread misuse of antibiotics. For decades medicinal chemists replenished the arsenal of antibiotics by semisynthetic and to a lesser degree fully synthetic routes, but economic factors have led to a subsidence of this effort, which places society on the precipice of a disaster. We believe that the strategic application of modern chemical synthesis to antibacterial drug discovery must play a critical role if a crisis of global proportions is to be averted.

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“…[113] Weitere Verbesserungen im Anschluss (häufige Dosierung ist auch bei Meropenem notwendig) führten 2001 zur Zulassung eines anderen vollsynthetischen C1-b-Methylcarbapenems, Ertapenem (Merck). [114] Carbapeneme sind nicht die einzigen vollsynthetisch hergestellten b-Lactame unter den wichtigen Antibiotika. 1981 beschrieben zwei Forschungsgruppen unabhängig voneinander die Isolierung monocyclischer b-Lactam("Monobactam")-Naturstoffe aus verschiedenen Bakterienstämmen.…”

Section: Vollsynthetische Antibakterielle Chinoloneunclassified

Zur Rolle der chemischen Synthese in der Entwicklung antibakterieller Wirkstoffe

2014

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Die Entdeckung und Einführung der Antibiotika im frühen zwanzigsten Jahrhundert hatte gewaltige Auswirkungen auf das Gesundheitwesen. Die chemische Synthese ermöglichte die Entwicklung der ersten antibakteriellen Substanzen, Organoarsenverbindungen und Sulfa‐Medikamente, die jedoch bald von wirksameren und weitaus komplexeren natürlichen Antibiotika verdrängt wurden: unter anderem Penicillin, Streptomycin, Tetracyclin und Erythromycin. Diese ersten Abwehrstoffe sind inzwischen – als unvermeidbare Folge der raschen Resistenzentwicklung bei pathogenen Bakterien – deutlich weniger wirksam, was durch die weit verbreitete falsche Anwendung von Antibiotika noch verstärkt wurde. Jahrzehntelang ergänzten Medizinchemiker das Repertoire der Antibiotika durch semisynthetische und in geringerem Maße vollsynthetische Routen, aber ökonomische Faktoren haben einen Rückgang dieser Bemühungen ausgelöst, was die Gesellschaft an den Rand einer Katastrophe führt. Wir sind überzeugt, dass die strategische Anwendung moderner chemischer Synthesemethoden zur Entwicklung antibakterieller Wirkstoffe von entscheidender Bedeutung ist, wenn eine globale Krise abgewendet werden soll.

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Practical Synthesis of the New Carbapenem Antibiotic Ertapenem Sodium

Cited by 29 publications

References 37 publications

Using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry To Detect Carbapenem Resistance within 1 to 2.5 Hours

Using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry To Detect Carbapenem Resistance within 1 to 2.5 Hours

The Evolving Role of Chemical Synthesis in Antibacterial Drug Discovery

Zur Rolle der chemischen Synthese in der Entwicklung antibakterieller Wirkstoffe

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