Franco Fernández

Bovine rotavirus strains circulating in beef and dairy herds in Argentina from 2004 to 2010

Bovine Group A Rotavirus (RVA) is one of the main causes of neonatal calf diarrhea worldwide. The present study reports the genotyping of bovine RVA strains circulating in Argentinean cattle from 2004 to 2010. Additionally, a new set of typing primers was designed and tested to differentiate between G8 and G6 (lineage III and IV) RVA strains. Bovine RVA was detected in 30% (435/1462) of the tested samples, corresponding to 49% (207/423) of the studied outbreaks with a similar detection rates in beef (53%; 67/127) and dairy herds (52%; 65/126). The RVA strains circulating in Argentinean cattle belonged to the common bovine genotypes G6 (lineages III and IV), G8, G10, P[5] and P[11]. A different RVA G/P-genotype distribution was found between the exploitation types, with the combination G6(IV)P[5] being by fare the most prevalent RVA strain in beef herds (58%), whereas a more even distribution of G6(III)P[11] (15%), G10P[11] (17%), G6(IV)P[5] (14%), and G6(IV)P[11] (6%) RVA strains was detected in dairy herds. G8 RVA strains were found in two dairy farms in calves co-infected with G8+G6(III)P[11]. A high percentage of co-infections and co-circulation of RVA strains with different genotypes during the same outbreak were registered in both exploitation types (20% of the outbreaks from beef herds and 23% from dairy herds), indicating a potential environment for reassortment. This finding is significant because G10P[11] and G6(III)P[11] strains may possess zoonotic potential. Continuous surveillance of the RVA strains circulating in livestock provides valuable information for a better understanding of rotavirus ecology and epidemiology.

Synthesis, antiviral and cytostatic activities, of carbocyclic nucleosides incorporating a modified cyclopentane ring. IV. Adenosine and uridine analogues.

ABSTRACT Eight new carbocyclic nucleosides were prepared by mounting a purine (compounds 8–10), 8-azapurine (12 and 13) or pyrimidine (15, 16 and 17b) on the amino group of (1S,3R)-3-aminomethyl-2,2,3-trimethylcyclopentylmethanol (6). All the compounds were evaluated as antiviral and antitumor agents in a variety of assay systems. Only compound 8 showed any cytostatic activity against the tumor cell lines examined.

Enantioselective synthesis of 3-functionalized 2-azabicyclo[2.2.1]hept-5-enes by hetero Diels-Alder addition to cyclopentadiene

Abstract Diels-Alder cycloaddition of N -benzyl imine of (1 R )-8-phenylmenthyl glyoxylate to cyclopentadiene gave the mixture of adducts 3a-d . Major diastereoisomer, the (1 S , exo )-adduct ( 3a ), was isolated in 57% yield and transformed in 74% overall yield into (+)-(1 S )- N -benzoyl-2-azabicyclo-[2.2.1]heptan-3-one ( 8 ), which was compared with an authentic sample of its enantiomer. In the course of this transformation sequence, the chiral auxiliary (1 R )-8-phenylmenthol was recovered in 90% yield.

Synthetic approaches to (1S,3R)-3-aminomethyl-2,2,3-trimethylcyclopentylmethanol and (1S,3R)-3-amino-2,2,3-trimethylcyclopentylmethanol from (+)-camphoric acid

Abstract The title aminomethyl ( 5 ) and amino ( 6 ) alcohols, which are of interest as intermediates in the synthesis of carbocyclic analogues of nucleosides, were prepared from (+)-camphoric acid via methyl (1 S ,3 R )-3-carbamoyl-2,3,3-trimethylcyclopentane carboxylate ( 8 ). Direct reduction of 8 gave 5 in 26% yield. Amino alcohol 6 was prepared in 11–53% overall yields by several approaches, each involving oxidative degradation of 8 followed by a reduction step.

A short, efficient synthesis of the chiral auxiliary (+)-8-phenylneomenthol

Abstract (+)-8-Phenylneomenthol 2, the structure of which was confirmed by X-ray analysis of its 3,5-dinitrobenzoate, was efficiently prepared from commercially available (−)-8-phenylmenthol 3 by oxidation with the Sarett reagent, followed by L-Selectride reduction of the (+)-8-phenylmenthone 6 thus formed.

Synthesis of novel carbocyclic nucleosides with a cyclopentenyl ring: Homocarbovir and analogues

Abstract Several synthetic strategies have been used to prepare (±)-cis-4-(aminomethyl)-2-cyclopentenylmethanol (6) from norbornadiene. Amino alcohol 6 has been then used to prepare an homologue of carbovir and its congeners. Alternatively, a synthetic intermediate in the preparation of 6 can be used in a convergent mode to prepare the corresponding adenine and inosine analogues.

A Useful Synthesis of Chiral Glyoxylates

Abstract A convenient synthesis of the cyclohexyl, (1R,3R,4S)-3-P-menthyl and (15-endo)-2-bomyl glyoxylates, from the respective alcohols and other very available materials, as a model applicable to that of other chiral, sensitive giyoxylates, is described.

Synthesis and characterization of all stereoisomers of 8-phenylmenthol

Abstract New, improved and/or specific syntheses of the diastereoisomers of (−)-8-phenylmenthol are described. The configurations of these products, usable as chiral auxiliaries, were confirmed by X-ray diffractometry of their 3,5-dinitrobenzoates.

Synthesis of novel 1-alkyl-8-substituted-3-(3-methoxypropyl) xanthines as putative A2B receptor antagonists

In order to identify a high-affinity, selective antagonist for the A(2B) subtype adenosine receptor, more than 40 1,8-disubstituted-3-(3-methoxypropyl) xanthines were prepared and evaluated for their binding affinity at recombinant human adenosine receptors, mainly of the A(2A) and A(2B) subtypes. Some of the 1-ethyl-3-(3-methoxypropyl)-8-aryl substituted derivatives 15(a-m) showed moderate-to-high affinity at human A(2B) receptors, with compound 15d showing A(2B) selectivity over the other A receptors assayed (A(1), A(2A), A(3)) of 34-fold or over.

Multicomponent Assembly of Diverse Pyrazin-2(1H)-one Chemotypes

An expedient and concise Ugi-based approach for the rapid assembly of pyrazin-2(1H)-one-based frameworks has been developed. This convergent approach encompasses skeletal, functional and stereochemical diversity, exhibiting an unusually high bond-forming efficiency as well as high structure and step economies. The method involves the use of readily available commercial reagents and is an example of the reconciliation of structural complexity with operational simplicity in a time- and cost-effective manner.