Sandra Ribes

2-Functionalized furans as precursors of versatile cycloheptane synthons

Abstract An study on the influence of steric and electronic effects of a function attached at C-2 of furans in the yield and diastereoselectivity of [4 + 3] cycloaddition reactions with oxyallyl cations is presented. In almost all studied furans a cis diastereospecificity and a high endo diastereoselectivity is observed. Increasing bulkyness of the function attached at C-2 of furans, the endo diastereoselectivity increases, but yield decreases. Increasing the electronic density of the furan system, by an electron donating group at C-2, both yield and diastereoselectivity increase.

General method of assignment of relative stereochemistry in C‐1‐substituted 2,4‐dimethyl‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐one by 1H and 13C NMR correlations

The 1H and 13C NMR spectra of cis‐endo (a) and cis‐exo (b) diastereoisomeric pairs of five differently C‐1‐functionalized 2,4‐dimethyl‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐ones were completely assigned. Several trends regarding the variation of chemical shifts and coupling constants of hydrogen and carbon atoms, on changing the configuration at C‐2 and C‐4 in both diastereoisomers, were observed by correlation of spectral data: methyl groups attached at C‐2 and C‐4 in a appear in 1H NMR at higher field than in diastereoisomer b. Simultaneously, H‐2 and H‐4 result in a lower field in a than in b. Both effects are due to the different interactions of hydrogens H‐2, H‐4, H‐9 and H‐10 with the bridging oxygen. In 13C NMR spectra it is possible to observe an upfield shift of C‐9, C‐10 and C‐3 in b versus a. The difference observed in chemical shifts of the aforementioned hydrogens and carbons, between both diastereoisomers, allows one to assign the configuration at C‐2 and C‐4 in such structures. This phenomenon has wide scope and validity and could be applied to the stereochemical determination of any pair of diastereoisomers (a and b), independently of the function attached to C‐1 of the oxabicyclic system. ©1998 John Wiley & Sons, Ltd.

Meningitis experimental producida por una cepa de Streptococcus pneumoniae serotipo 23F con elevada resistencia a cefalosporinas

Introduccion El aumento de cepas de Streptococcus pneumoniae con elevada resistencia a cefalosporinas supondria un problema en el tratamiento de las infecciones graves como la meningitis. Existen interrogantes sobre las caracteristicas de estas cepas, como su capacidad para producir infecciones o la respuesta inflamatoria que generan en el liquido cefalorraquideo Metodos Utilizando el modelo de meningitis neumococica en conejo, se estudio la patogenicidad y las posibles diferencias en determinados parametros inflamatorios de dos cepas de S. pneumoniae del serotipo 23F con distinta sensibilidad a betalactamicos. Las concentraciones inhibitorias minimas fueron: cepa A (penicilina, 4=g/ml; ceftriaxona/cefotaxima, 2μg/ml); y cepa B (penicilina, 0,12μg/ml; ceftriaxona/cefotaxima, 32μg/ml) Resultados La cepa A mostro una mayor presencia de bacteriemia secundaria y parametros inflamatorios superiores en las primeras etapas de la infeccion. La cepa B produjo edema cerebral, y mayor mortalidad y actividad inflamatoria a la hora 24 Conclusiones Ambas cepas generaron meningitis en el modelo animal. Las diferencias en la respuesta inflamatoria producida por las dos cepas podrian estar relacionadas con las variaciones que determinan el grado de resistencia a betalactamicos

Contribution of capsular and clonal types and β-lactam resistance to the severity of experimental pneumococcal meningitis

We used a rabbit model to assess the effects of capsular serotype, genetic background and beta-lactam resistance on the course and severity of experimental meningitis. Meningitis was induced by five pneumococcal strains belonging to five different clones with known invasive potential: two serotype 3 strains (ST260(3) and Netherlands(3)-31 clones) and three serotype 23F strains with different beta-lactam susceptibility patterns (Spain(23F)-1 clone, Tennessee(23F)-4 clone and a double locus variant of the Tennessee(23F)-4 clone). Major differences in secondary bacteremia and mortality rates were observed between serotypes 3 and 23F, as were divergences in the CSF lactate, protein and lipoteichoic-teichoic acid concentrations. Minor differences in the CSF-induced inflammatory response were found among strains belonging to the same serotype. Our results suggest that capsular serotype might be the main factor determining the course and severity of pneumococcal meningitis and genetic background contributes to a lesser extent. The acquisition of beta-lactam resistance does not reduce the virulence of the invasive clones. Since five strains belonging to two serotypes were studied, our findings have to be confirmed with other pneumococcal serotypes.

Experimental study of clinafloxacin alone and in combination in the treatment of ciprofloxacin-susceptible and -resistant pneumococcal meningitis.

The increasing incidence of ciprofloxacin resistance in Streptococcus pneumoniae may limit the efficacy of the new quinolones in difficult-to-treat infections such as meningitis. The aim of the present study was to determine the efficacy of clinafloxacin alone and in combination with teicoplanin and rifampin in the therapy of ciprofloxacin-susceptible and ciprofloxacin-resistant pneumococcal meningitis in rabbits. When used against a penicillin-resistant ciprofloxacin-susceptible strain (Clinafloxacin MIC 0.12 microg/ml), clinafloxacin at a dose of 20 mg/kg per day b.i.d. decreased bacterial concentration by -5.10 log cfu/ml at 24 hr. Combinations did not improve activity. The same clinafloxacin schedule against a penicillin- and ciprofloxacin-resistant strain (Clinafloxacin MIC 0.5 microg/ml) was totally ineffective. Our data suggest that a moderate decrease in quinolone susceptibility, as indicated by the detection of any degree of ciprofloxacin resistance, may render these antibiotics unsuitable for the management of pneumococcal meningitis.