Synthesis, HPLC enantioresolution and X-ray analysis of a new series of C5-methyl pyridazines as N-formyl peptide receptor (FPR) agonists

The synthesis of three racemates and the corresponding non chiral analogues of a C5-methyl pyridazine series is described here, as well as the isolation of pure enantiomers and their absolute configuration assignment. In order to obtain optically active compounds, direct chromatographic methods of separation by HPLC-UV were investigated using four chiral stationary phases (CSPs: Lux Amylose-2(®), Lux Cellulose-1(®), Lux Cellulose-2(®) and Lux Cellulose-3(®)). The best resolution was achieved using amylose tris(5-chloro-2-methylphenylcarbamate) (Lux Amylose-2(®)), and single enantiomers were isolated on a semipreparative scale with high enantiomeric excess, suitable for biological assays. The absolute configuration of optically active compounds was unequivocally established by X-ray crystallographic analysis and comparative chiral HPLC-UV profile. All compounds of the series were tested for formyl peptide receptor (FPR) agonist activity, and four were found to be active, with EC(50) values in the micromolar range

Rehabilitación de ambientes perdidos en megaciudades: el caso de la Cuenca Matanza-Riachuelo

La tendencia a degradar o reemplazar la matriz natural (clímax) por sistema agropecuarios o viviendas humanas es tan extensa e intensa, que también está afectando a otros componentes del paisaje como los corredores ribereños y sus humedales asociados, ambientes edáficos, locales, de alta sensibilidad ecológica, así como a diversos parches y remanentes naturales en zonas de alta incidencia urbana. El objeto central de este capítulo será analizar los procesos de rehabilitación ecológica en la cuenca Matanza-Riachuel

Candidurie nosocomiali: analisi dei fattori di rischio, terapia ed evoluzione micologica. Risultati di una indagine nazionale

The multiple problems associated with the recovery of yeasts from urine specimens induced the Medical Mycology Committee (CoSM) of AMCLI to run a nationwide epidemiologic survey on candiduria in order to evaluate risk factors, involved species, treatment and outcome. Ten hospitals (Bergamo, Como, Crema, Novara,Varese,Ancona, Florence, Pescara, Palermo and Taranto) participated to this study, which was run on a 15-month period (October 1, 2001-December 31, 2002). Overall, 83 Data Forms were collected, regarding patients admitted to Intensive Care Units (45), Surgical (9) and Medical (29) wards. The most common risk factors were: bladder catheter, antibiotic therapy, parenteral nutrition, kidney failure, surgery. Candiduria, mostly asymptomatic, were often associated with fever and bacterial infections. Concurrent candidaemia was detected in 13 patients. Candida albicans was the most frequently recovered species, from both urine and blood, followed by C. glabrata. Other Candida species were occasionally isolated from urine specimens. Specific antifungal treatment was administered to 58% of the patients, mostly using fluconazole. The remaining subjects did not receive antimycotic therapy. Eradication of Candida from urine specimens was observed even without a specific therapy

A chromatographic study on the exceptional chiral recognition of 2-(benzylsulfinyl)benzamide by animmobilized-type chiral stationary phase based on cellulose tris(3,5-dichlorophenylcarbamate)

In previous studies, Okamoto et al. described the results of the exceptionally large chiral recognitionof 2-(benzylsulfinyl)benzamide onto a coated-type chiral stationary phase based on cellulose tris(3,5-dichlorophenylcarbamate). As a continuation and deepening of those studies, here the sulfoxide and asmall set of its structural analogues were analyzed on the commercially available Chiralpak IC-3 chiralstationary phase based upon the same polysaccharide derivative as the chiral selector but immobilizedonto silica support.The chromatographic results obtained using different mobile phases consisting of pure methanol,ethanol and 2-propanol or binary mixtures n-hexane-2-propanol, which are prohibited with the pro-genitor coated-type chromatographic support, permitted to identify the NH2of the amide group as thekey structural element of the (S)-enantiomer of 2-(benzylsulfinyl)benzamide for obtaining a very highaffinity for the IC-3 chiral stationary phase

Cycloaddition Reactions of C,N-Diphenylnitrone to Methylene-γ-butyrolactones

Cycloaddition of C,N-diphenylnitrone to α-methylene-γ-butyrolactone afforded two diastereomeric 5-spirosubstituted isoxazolidines with high selectivity. Structural assignment was ascertained by NMR studies and an X-ray diffraction experiment on a single crystal of the major isomer and the diastereoselectivity was rationalized on examination of the alternative transition states leading to the two diastereoisomers

Total Synthesis of Bruceolline I

The first total synthesis of the natural product bruceolline I, isolated in small quantities from the ethanol extract of <i>Brucea mollis</i> stems, was achieved in 29% yield over nine steps and with high enantiomeric purity (>98%). The key step of the process is the tandem gold-catalyzed rearrangement/Nazarov reaction of a propargylic acetate derivative. This synthesis provides a sufficient amount of synthesized bruceolline I for further bioassays

Application of an immobilised amylose-based chiral stationary phase to the development of new monoamine oxidase B inhibitors

A direct HPLC enantioseparation of three new chiral oxadiazoline derivatives endowed with potential MAO-B inhibitory activity was accomplished on the immobilised Chiralpak IA chiral stationary phase. Multi-mg amounts of enantiomers with high enantiomeric purity (ee >= 98%) were rapidly collected using pure dichloromethane as eluent. The absolute configuration and chiroptical properties of the enantiomers isolated at semipreparative scale were exhaustively determined