Transformations using benzyl 6-isocyanopenicillanate

Bentley, P. H.; Clayton, J. P.; Boles, M. O.; Girven, Richard J.

doi:10.1039/p19790002455

Cited by 27 publications

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“…Among the cephalosporins and related f8-lactams, increased stability to f-lactamase has been achieved in a number of compounds (7,8), including cefuroxime and cefoxitin, as well as certain newer members such as cefotaxime, moxalactam, and ceftazidime (GR 20263), and this stability is reflected in the antibacterial activity of these compounds against the fl-lactamaseproducing organisms. In the penicillin family, however, attempts to achieve f3-lactamase stability together with adequate antibacterial activity against gram-negative organisms have, so far, met with only limited success. This report describes a new semisynthetic ,Blactam antibiotic, in which a methoxy group has been introduced at the 6a-position in the nucleus (2). This compound, BRL 17421, 6f3-(2-carboxy-2-thien-3-yl acetamido)-6a-methoxypenicillanic acid, disodium salt ( Fig.…”

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confidence: 99%

BRL 17421, a novel beta-lactam antibiotic, highly resistant to beta-lactamases, giving high and prolonged serum levels in humans

Slocombe¹,

Basker²,

Bentley³

et al. 1981

Antimicrob Agents Chemother

130

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BRL 17421 is a new semisynthetic beta-lactam antibiotic with an unusual spectrum of antibacterial activity. The compound exhibits exceptional stability to a wide range of bacterial beta-lactamases and is active against the majority of Enterobacteriaceae, including strains highly resistant to many of the penicillins and cephalosporins currently available. Among the clinical isolates of Enterobacteriaceae tested, the frequency of strains resistant to BRL 17421 was found to be low, and there was a slow rate of emergence of resistance during in vitro studies. BRL 17421 was highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase-producing strains. The compound was markedly less active against Pseudomonas aeruginosa and Bacteroides fragilis than against the Enterobacteriaceae. Against the gram-positive bacteria, BRL 17421 showed a very low level of activity. BRL 17421 was found to be 85% bound to human serum, and the antibacterial activity was diminished two- to fourfold in the presence of human serum. Against experimental infections in mice, the activity of BRL 17421 reflected the properties observed in vitro. Studies in human volunteers showed unusually high and prolonged serum concentrations of the compound after parenteral dosage, with a serum half-life of about 5 h, and approximately 85% of the dose was recovered unchanged in the urine. BRL 17421 was poorly absorbed after oral administration. The compound was well tolerated after intramuscular and intravenous administration in volunteers, with no adverse side effects.

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mentioning

confidence: 99%

BRL 17421, a novel beta-lactam antibiotic, highly resistant to beta-lactamases, giving high and prolonged serum levels in humans

Slocombe¹,

Basker²,

Bentley³

et al. 1981

Antimicrob Agents Chemother

130

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“…Acylation of (6S)-benzyl6-amino-6-(methylthio)penicillanate (6) with (R)-2-azido-2-phenylacetyl chloride in the presence of pyridine gave the R-side-chain isomer (7) as the sole product.…”

Section: H Ph Cozchzph ( 6 )mentioning

confidence: 99%

Spirocyclic penicillins

Burton¹,

Harrington²

1987

J. Chem. Soc., Perkin Trans. 1

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“…bei der Chromatographie an Kieselgel oder beim Stehen in HC1-haltigem CDCl, das P-Lactam gespalten und das entsprechende 4,5-Dihydro-5-(methylthio)-1,3-thiazo13 zuruckgebildet. Umsetzung von 8a mit Phenylessigsaure-chlorid und Et,N lieferte in Analogie zu [34] in 63 YO Ausbeute das Amid 9 (Schema 4 ) . Zur Berechnung wurden 88 automatisch zentrierte Reflexe einer Hemisphare rnit 41 < 1281 < 49" verwendet.…”

Section: ' )unclassified

Synthese von (Methylthio)penam‐Derivaten durch Keten‐Addition an 4,5‐Dihydro‐5‐(methylthio)‐1,3‐thiazole

Jenny

Prewo

Bieri

et al. 1986

Helvetica Chimica Acta

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Synthesis of (Methy1thio)penam Derivatives via Keten Addition onto 4,5-Dihydro-5-(methyIthio)-l,3-thiazolesThe 4,5-dihydro-5-(methyIthio)-2-phenyl-1,3-thiazoles 3a and 3b, easily prepared from the corresponding 1,3-thiazol-5(4H)-thiones and MeLi, react with dichloroacetyl chloride (5a) and acidoacetyl chloride (5b) in the presence of Et,N to give (methy1thio)penam derivatives 6 ( Table 1). The reaction mechanism is either a [2 + 21 cycloaddition of in situ generated ketene or a two-step reaction (Scheme 2). The structure of 6f has been confirmed by X-ray crystallography (Fig.2). The relative configuration of 6a+2 follow from comparison of their 'H-NMR spectra with those of 6f (Fig. I). The 6-addopenams 6d and 6f have been reduced to aminopenams 8a and 8b, respectively. Acylation of 8a with phenacetyl chloride yields 9 (Scheme 4 ) .

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Transformations using benzyl 6-isocyanopenicillanate

Cited by 27 publications

References 0 publications

BRL 17421, a novel beta-lactam antibiotic, highly resistant to beta-lactamases, giving high and prolonged serum levels in humans

BRL 17421, a novel beta-lactam antibiotic, highly resistant to beta-lactamases, giving high and prolonged serum levels in humans

Spirocyclic penicillins

Synthese von (Methylthio)penam‐Derivaten durch Keten‐Addition an 4,5‐Dihydro‐5‐(methylthio)‐1,3‐thiazole

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