Graciela Y. Moltrasio

Silica-supported heteropolyacids as catalysts in alcohol dehydration reactions

Catalysts based on Keggin-type heteropolyacids supported on silica were prepared for their use in dehydration of alcohols in liquid phase. Species present in the catalysts were characterized by diverse physicochemical techniques, disclosing that both molybdophosphoric and tungstophosphoric acids are found with their primary Keggin structure intact. Their catalytic behavior was studied in the dehydration of alcohol of interest for the production of intermediary compounds for fine chemical industries. Specifically, the dehydration of 1,2-diphenylethanol, 1-(3,4-dimethoxyphenyl)-2-phenylethanol and cholesterol was studied. It was obtained a process for the direct dehydration of cholesterol. It was found that the catalysts are very active and selective, also allowing an easy separation from the reaction medium. The same catalysts were used several times without appreciable loss of catalytic activity and after the reaction they showed physicochemical properties similar to those of the original catalysts.

Inhibitory effect of thiosemicarbazone derivatives on Junin virus replication in vitro

The inhibitory effect of several thiosemicarbazones (TSCs), synthesized from aromatic ketones and terpenones, and their heterocyclic thiadiazoline (TDZ) derivatives, was investigated against Junin virus (JUNV), an arenavirus agent of Argentine haemorrhagic fever. From the 25 compounds tested, six compounds belonging to the TSC group were found to be selective inhibitors of JUNV, with EC50 values determined by a virus yield inhibition assay in the range 3.4–12.5 μM, and selectivity indices greater than 10. By contrast, most of the TDZs obtained by heterocyclization of the TSCs were not active against JUNV. No conclusive structure-activity relationships could be established but systematically higher activity was associated to TSCs derived from aromatic ketones. The mode of action of one of the most active compound, the 3,4-dihydronaphtalen-1(2H)one thiosemicarbazone (tetralone thiosemicarbazone), was studied further. This TSC lacked virucidal effects on JUNV virions. Results from time of addition experiments and viral protein expression assays suggest that tetralone thiosemicarbazone inhibited a late stage in the replicative cycle of JUNV.

Thiosemicarbazones derived from 1-indanones as new anti-Trypanosoma cruzi agents

In the present work, we synthesized a series of thiosemicarbazones derived from 1-indanones with good anti-Trypanosoma cruzi activity. Most of them displayed remarkable trypanosomicidal activity. All the compounds showed nonspecific cytotoxicity on human erythrocytes. The ability of the new compounds to inhibit cruzipain, the major cysteine protease of T. cruzi, was also explored. Thiosemicarbazones 12 and 24 inhibited this enzyme at the dose assayed. This interaction was also studied in terms of molecular docking.

Stereoselective synthesis of cyclobutyl GABA analogues and related compounds from (-)-(S)-verbenone

Abstract The highly stereoselective conjugate addition of nitromethane to α,β-unsaturated cyclobutyl esters derived from (−)-(S)-verbenone has been executed to afford the adducts as single stereoisomers in good yields. These products furnish cyclobutyl GABA analogues and γ-lactams which, in turn, can be used as precursors of pyrrolidines. Moreover, both the enantiopure γ-nitro esters and the derived γ-amino esters are potentially useful for incorporation into γ-amino peptidomimetics.

Inhibition of Bovine Viral Diarrhea Virus RNA Synthesis by Thiosemicarbazone Derived from 5,6-Dimethoxy-1-Indanone

ABSTRACT In the present work, we described the activity of the thiosemicarbazone derived from 5,6-dimethoxy-1-indanone (TSC), which we previously characterized as a new compound that inhibits bovine viral diarrhea virus (BVDV) infection. We showed that TSC acts at a point of time that coincides with the onset of viral RNA synthesis and that it inhibits the activity of BVDV replication complexes (RCs). Moreover, we have selected five BVDV mutants that turned out to be highly resistant to TSC but still susceptible to ribavirin (RBV). Four of these resistant mutants carried an N264D mutation in the viral RNA-dependent RNA polymerase (RdRp). The remaining mutant showed an A392E mutation within the same protein. Some of these mutants replicated slower than the wild-type (wt) virus in the absence of TSC, whereas others showed a partial reversion to the wt phenotype over several passages in the absence of the compound. The docking of TSC in the crystal structure of the BVDV RdRp revealed a close contact between the indane ring of the compound and several residues within the fingers domain of the enzyme, some hydrophobic contacts, and hydrogen bonds with the thiosemicarbazone group. Finally, in the mutated RdRp from resistant BVDV, these interactions with TSC could not be achieved. Interestingly, TSC inhibited BVDV replication in cell culture synergistically with RBV. In conclusion, TSC emerges as a new nonnucleoside inhibitor of BVDV RdRp that is synergistic with RBV, a feature that turns it into a potential compound to be evaluated against hepatitis C virus (HCV).

Synthesis and antifungal activity of some substituted phenothiazines and related compounds

Several phenothiazines and related compounds were synthesized and their antifungal activity was evaluated in vitro. The results observed for α-chloro-N-acetyl phenothiazine led us to choose this compound as a lead in the search of antifungal agents.

Antibacterial and antifungal activity of some thiosemicarbazones and 1,3,4-thiadiazolines

A series of thiosemicarbazones and thiadiazolines was evaluated for biological activity against various microorganisms such as Bacillus subtilis, Micrococcus luteus, Listeria monocytogenes, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, Trichophyton mentagrophites and Aspergillus niger. Some of the assayed compounds showed interesting activity against Bacillus subtilis, Candida albicans, Micrococcus luteus, Trichophyton mentagrophites and Aspergillus niger

Stereoselective synthesis of chiral precursors to cyclobutane carbocyclic nucleosides and oligopeptides

Abstract Versatile and highly efficient synthetic routes leading to optically active cyclobutanones, γ-amino acids and δ-amino alcohols are described. These compounds are relevant synthetic precursors to enantiopure cyclobutane carbocyclic nucleosides and oligopeptides. (−)-(S)-Verbenone is the chiral starting material used and the key synthetic steps involve concerted rearrangements in acidic medium.

A Formal [3 + 2] Alkene Addition to Benzhydrol Cations. A Practical and Mild Methodology for the Synthesis of Substituted 1‐Arylindanes and Related Compounds

Abstract We report the single step synthesis of several 1‐arylindanes in good yield via a formal [3 + 2] atom cycloaddition. The success of this formal cycloaddition relies on the Lewis acid activation of a bibenzylic alcohol in the presence of an alkene. The cation generated from the alcohol can be trapped by the alkene to afford a new benzylic cation which can then undergoes cyclization leading to 1‐arylindanes with three stereogenic centres.

SILICA-SUPPORTED HETEROPOLYACIDS READILY INDUCE CYCLODIMERIZATION OF STYRENES AND STILBENES

ABSTRACT Heteropolyacids such as molybdophosphoric and tungstophosphoric acids, supported over silica, readily induce cyclodimerisation reactions of styrenes and stilbenes affording a mixture of indane and/or tetraline derivatives with remarkably high efficiency and in reduced reaction time.