ChemInform Abstract: SYNTHETIC ANALOGS OF β‐LACTAM ANTIBIOTICS. BIOLOGICALLY ACTIVE 2‐ALKYLIDENE‐3‐DEACETOXYMETHYL CEPHALOSPORINS

Woodward, R. B.; Heusler, K.; Ernest, I.; Burri, K.; Friary, R.; Haviv, Fortuna; Oppolzer, Wolfgang; Paioni, R.; Syhora, K.; Wenger, Roland M.; Whitesell, James K.

doi:10.1002/chin.197724397

Cited by 4 publications

(7 citation statements)

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“…A stabilized phosphorane grouping was next built up on the azetidinone N-atom of 3 using a three-step method developed in these laboratories [3]. Reaction of 3 with (hydrated) t-butyl glyoxylate in the presence of activated molecular sieves gave the epimeric hemiaminals 4; these in turn were transformed, with thionyl chloride and a polymeric tertiary base, into the corresponding chlorides 5, which on warming with triphenylphosphine and the polymeric base afforded the phosphorane 6 in an over-all yield from 3 of 38%.…”

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confidence: 99%

2‐Oxocephems. Synthesis and Properties of 7‐Acylamino‐2‐oxocephem‐4‐carboxylic Acids

Ernest¹

1979

Helvetica Chimica Acta

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Dedicated to the memory of Prof. R. B. Woodward (4. IX. 79) SummaryA synthesis of (6 R, 7 R)-7-acylamino-2-oxocephem-4-carboxylic acids from penicillins is reported based on the formation of the 2-oxocephem system in an intramolecular Wittig condensation. An interesting steric effect of the acylamino grouping on the course of this key step was used to advantage. Some physical and biological properties of this new type of A3-cephem are described.The azetidinone ring of all known bicyclic 8-lactam antibiotics is more sensitive to opening by nucleophilic agents than are simple, monocyclic, azetidinones, and evidence is accumulating that this increased chemical reactivity is an important prerequisite to the outstanding antibacterial activity of these compounds.Some time ago, in the search for new systems with increased reactivity of the P-lactam ring, we considered 2-oxocephem-4-carboxylic acids 1, unknown at the time, to be promising candidates for our synthetic studies. We assumed that a delocalization of the free electron pair from the P-lactam N-atom into the double bond of the annulated, six-membered ring -certainly very incomplete in most A3-cephem derivatives -would become much more pronounced if the double bond were part of the electron-withdrawing system of 1 tf l a ; this should result in a strong activation of the P-lactam carbonyl group toward nucleophiles and might have interesting consequences for the biological activity of such compounds.Recently, based on similar reasoning, a synthesis of several 2-oxocephem-4-carboxylic acids 1 was described by Kim et al.[l] prompting us to publish our Scheme I $OOH

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confidence: 99%

2‐Oxocephems. Synthesis and Properties of 7‐Acylamino‐2‐oxocephem‐4‐carboxylic Acids

Ernest¹

1979

Helvetica Chimica Acta

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“…Column chromatography (S1O2, toluene-ethyl acetate (4:1)) gave 4.6 g of pure 7 (67%). The crystals had mp 94-95 °C: IR 2.97, 5.6, 6.05, 6.37, 6.85 µ; NMR 7.60 (m, 1), 7.22 (d, 1,7= 3.5 Hz), 6.85 (m, 1, exchanges with D2O), 6.55 (dd, 1,7 = 2 and 3.5 Hz), 2.95-3.65 (m, 2). Anal.…”

Section: Cooh Cooh La Lbmentioning

confidence: 99%

The penems, a new class of .beta.-lactam antibiotics. 2. Total synthesis of racemic 6-unsubstituted representatives

Lang¹,

Prasad²,

Holick³

et al. 1979

J. Am. Chem. Soc.

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“…In a three-step procedure developed in these laboratories [8], a stabilized phosphorane grouping was next built up on the azetidinone N-atom (14a-t 15a; 52% over three steps). Transformation of the crotonoylthio substituent of 15a into the glyoxyloylthio grouping necessary for the intramolecular Wittig reaction was achieved by low-temperature ozonization of 15a in methylene chloride in the presence of The described indirect way to 14a via the vinylacetylthio derivative 13a was necessary, since a.8-unsaturated thiocarboxylic S-acids.…”

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confidence: 99%

2‐Oxocephems and 2‐Acetylpenems ‐ Selective Formation in an Intramolecular Wittig Reaction

Ernest

Main

Woodward

1981

Helvetica Chimica Acta

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SummarySelective formation -in intramolecular Wittig condensations -of the 2-0x0-cephem-4-carboxylate 8 a and of the 2-acetylpenem-3-carboxylate 9, respectively, was observed as a consequence of different carbonyl reactivities in two homologous a-oxoacylthio groupings. Free, racemic and 7-unsubstituted 2-oxocephem-4-carboxylic acid (10) was prepared from 8a for biological testing. Attempts to prepare the free 2-acetylpenem-3-carboxylic acid from 9 failed, probably due to the high lability of the /I-lactam system.In our recently published synthesis of 7-acylamino-2-oxocephem-4-carboxylic acids 1 [ l ] [ 2 ] , a characteristic difference was observed in the behaviour of the glyoxyloylthio and the pyruvoylthio substituents, respectively, in the intramolecular Wittig condensations by which the novel bicyclic p-lactam system of 1 was formed. With the glyoxyloylthio phosphorane 2, the formation of the six-membered unsaturated thiolactone ring of 3 was straightforward due to the high reactivity of the formyl group. On the other hand, the S-ester carbonyl group of the pyruvoylthio phosphorane 4 competed successfully in the Wittig reaction with the ketonic

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ChemInform Abstract: SYNTHETIC ANALOGS OF β‐LACTAM ANTIBIOTICS. BIOLOGICALLY ACTIVE 2‐ALKYLIDENE‐3‐DEACETOXYMETHYL CEPHALOSPORINS

Cited by 4 publications

References 0 publications

2‐Oxocephems. Synthesis and Properties of 7‐Acylamino‐2‐oxocephem‐4‐carboxylic Acids

2‐Oxocephems. Synthesis and Properties of 7‐Acylamino‐2‐oxocephem‐4‐carboxylic Acids

The penems, a new class of .beta.-lactam antibiotics. 2. Total synthesis of racemic 6-unsubstituted representatives

2‐Oxocephems and 2‐Acetylpenems ‐ Selective Formation in an Intramolecular Wittig Reaction

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