Synthesis of some 1-oxa-1-dethiacephalosporins

Branch, Clive L.; Pearson, Michael J.

doi:10.1039/p19790002268

Cited by 22 publications

(10 citation statements)

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“…The oxygen analogue [62504- , (65, X = OH, R = ) of cefamandole 30 was as good as, or better than, cefamandole itself, except for activity against Proteus mirabilis (200). Other studies have demonstrated that the 1-oxa-dethiacephalosporins are for the most part comparable to, or slightly better than, the cephalosporin counterpart in antibacterial activity, although there are some exceptions, such as 1-oxa-dethiacephalexin [66204-07-7] (65, X = NH 2 , R = H), C 15 H 15 N 3 O 5 , which was inactive (201). Both the 1-oxa-dethiacephalosporins having a mandelamido C-7 side chain and either a methyl (65, X = OH, R = CH 3 ) or a hydrogen (65, X = OH, R = H) at C-3 had properties comparable to cephalexin 12 (201).…”

Section: Oxadethiacephalosporinsmentioning

confidence: 99%

“…Other studies have demonstrated that the 1-oxa-dethiacephalosporins are for the most part comparable to, or slightly better than, the cephalosporin counterpart in antibacterial activity, although there are some exceptions, such as 1-oxa-dethiacephalexin [66204-07-7] (65, X = NH 2 , R = H), C 15 H 15 N 3 O 5 , which was inactive (201). Both the 1-oxa-dethiacephalosporins having a mandelamido C-7 side chain and either a methyl (65, X = OH, R = CH 3 ) or a hydrogen (65, X = OH, R = H) at C-3 had properties comparable to cephalexin 12 (201). The effect of various substituents at C-3, C-7 β, acylamino side chains, and C-7α, methoxy and hydrogen, in the 1-oxa-dethiacephalosporin system have been extensively studied (194).…”

Section: Oxadethiacephalosporinsmentioning

confidence: 99%

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Cephalosporins

Roberts¹

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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CEPHALOSPORINSThe cephalosporins, a subgroup of β-lactam antibiotics, consist of a 4-membered lactam ring fused through the nitrogen and the adjacent tetrahedral carbon atom to a second heterocycle forming a 6-membered dihydrothiazine ring. Other structural features common to all the cephalosporins are a carboxyl group on the dihydrothiazine ring on the carbon next to the ring nitrogen and a functionalized amino group on C-7, the carbon of the β-lactam ring opposite the nitrogen. These features are evidenced in 7-aminocephalosporanic acid [957-68-6] (7-ACA), C 10 H 12 N 2 O 5 S 1. Cephalosporins, like all β-lactam antibiotics, exert their antibacterial effect by interfering with the synthesis of the bacterial cell wall. These antibiotics tend to be "irreversible" inhibitors of cell wall biosynthesis and they are usually bactericidal at concentrations close to their bacteriostatic levels. Cephalosporins are widely used for treating bacterial infections. They are highly effective antibiotics and have low toxicity.

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Section: Oxadethiacephalosporinsmentioning

confidence: 99%

Section: Oxadethiacephalosporinsmentioning

confidence: 99%

Cephalosporins

Roberts¹

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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“…D20), and 7.27 (1 H, d, J 10 Hz). (9) and (12).-t-Butyl glyoxylate monohydrate (3 g) was refluxed in benzene (15 ml) for 0.5 h with provision for the removal of water. The azetidinone (8) (250 mg) was added and the mixture refluxed for 13 h. The solvent was evaporated and the residue chromatographed to give the alcohol (9) as a thick oil (521 mg) (Found: M', 331.1083.…”

Section: (E)and (2)-4-( 2-ethoxycarbonylvinylthio)azetidin-2-onementioning

confidence: 99%

“…3 500, 3 420, 1 790, 1 750, and 1 690 cm-'. (27).-The hydroxy ester (26) (352 mg) was converted into the wide (27) as described for (9). The product (27) was a viscous gum (292 mg), vmaX.…”

Section: (3s4s)-(23) and (3s4r)-3-phenoxyacetamido-4-prop-2-enyloxyaz...mentioning

confidence: 99%

Synthesis of novel fused β-lactams by intramolecular 1,3-dipolar cycloadditions. Part 10. The 9-oxo-6-thia-1,3-diazabicyclo[5.2.0]nonene, 8-oxo-5-thia-1,3-diazabicyclo[4.2.0]octene, and 8-oxo-5-oxa-1,3-diazabicyclo[4.2.0]octene ring systems

Branch¹,

Pearson²

1986

J. Chem. Soc., Perkin Trans. 1

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“…The synthesis of optically active 3-methyl 1-oxacephems exhibiting antibacterial activity was first carried out by BRANCH and PEARSON.5,6) In previous papers, we have reported the synthesis of optically active 3-methyl 1-oxacephems,7)…”

mentioning

confidence: 99%

Synthesis and antibacterial activity of 1-oxacephem derivatives.

Narisada¹,

Yoshida²,

Onoue

et al. 1982

J. Antibiot.

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A number of new optically active 1-oxacephem compounds were synthesized and tested for antibacterial activity. Various 7a-unsubstituted 1-oxacephem nuclei 2a-e and a 7a-methoxy-1-oxacephem nucleus 3, reported previously, were converted into the corresponding phenylacetylamino-, 2-thienylacetylamino-, n-mandelylamino-, D-phenylglycylamino-, and arylmalonylamino-l-oxacephem carboxylic acids. All the compounds except for the phenylglycylamino derivatives exhibited four-to sixteen-fold enhanced antibacterial activity compared with that of the corresponding cephalosporins.A combination of the 7a-methoxy-3-(1-methyl-lH-tetrazol-5-yl)thiomethyl-l-oxacephem nucleus and a 7~-arylmalonylamino side chain, as represented by compound 1 (disodium salt of 33), produced the highest efficacy among them: high antibacterial activity with a widely expanded spectrum against Gram-negative bacteria including resistant strains and Pseudonronas aeruginosa was observed.Recently, increasing efforts to obtain better i9-lactam antibiotics have been focused on the synthesis of cephalosporin nuclear analogues in which the sulfur atom is replaced by either another atom or a group of atoms. CHRISTENSEN and co-workers first reported preparation of racemic 1-oxacephalothin1) and 1-oxacefamandole2) as well as some 1-carbacephems2,3) exhibiting significant antibacterial activity.WOLFE et al. reported4) the synthesis of an optically active 3-methyl 1-oxacephem ester but did not comment on the antibacterial activity of the compound. The synthesis of optically active 3-methyl 1-oxacephems exhibiting antibacterial activity was first carried out by BRANCH and PEARSON.5,6) In previous papers, we have reported the synthesis of optically active 3-methyl 1-oxacephems,7)which exhibit four-to eight-fold higher antibacterial activity than that of the corresponding cephalosporins, as well as the synthesis8~10) and structure-activity relationships8~11) of some 3-substituted-methyl 1-oxacephems including 7a-methoxy derivatives. Since then, several improved synthetic routes to 1-oxacephem nuclei have been reported from our laboratories,12~18) while other research groups have also reported on syntheses19~23) and the antibacterial activity21) of 1-oxacephem derivatives.In the present paper, we report in detail on chemical modifications at the C-73 position in 1-oxacephems as well as a novel method for introducing an arylmalonyl group into a 7a-methoxy 1-oxacephem nucleus. Investigation of the effect of C-3, C-7a, and C-7(3 groups upon the in vitro antibacterial activity of the resulting 1-oxacephems including latamoxef (1, moxalactam, 6059-S, LY127935), is also discussed. ChemistrySeveral series of 7j3-acylamino-l-oxacephems were prepared from the previously reported 7a-unsubstituted i-oxacephem nuclei 2a,7) 2b-e8) (Table 1) and the 7a-methoxy-l-oxacephem nucleus 38)

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Synthesis of some 1-oxa-1-dethiacephalosporins

Cited by 22 publications

References 0 publications

Cephalosporins

Cephalosporins

Synthesis of novel fused β-lactams by intramolecular 1,3-dipolar cycloadditions. Part 10. The 9-oxo-6-thia-1,3-diazabicyclo[5.2.0]nonene, 8-oxo-5-thia-1,3-diazabicyclo[4.2.0]octene, and 8-oxo-5-oxa-1,3-diazabicyclo[4.2.0]octene ring systems

Synthesis and antibacterial activity of 1-oxacephem derivatives.

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