Renzo Ruzziconi

Synthesis of unsymmetrical 1,4-diketones by the ceric ammonium nitrate promoted cross-coupling of trimethylsilyl enol ethers

Abstract Unsymmetrical 1,4-diketones are prepared in good yields (60–80%) by cerium (IV) ammonium nitrate oxidative cross-coupling between 1,2-disubstituted and 1-substituted trimethylsilyl enol ethers.

Synthesis of 1,4-dicarbonyl compounds by the ceric ammonium nitrate promoted reaction of ketones with vinyl and isopropenyl acetate

Abstract 1,4-diketones and 4-ketoaldehydes dimethylacetals can be prepared in good yields (65%–82%) by the cerium(IV) ammonium nitrate promoted reaction of ketones with isopropenyl acetate and vinyl acetate, respectively.

γ-selectivity in the ceric ammonium nitrate promoted oxidative addition of silyl dienol ethers to silyl enol ethers

Abstract Trimethylsilyl dienol ethers are easily oxidized by ceric ammonium nitrate to give α-carbonylallyl radicals which are able to add to enolic carbon-carbon double bonds with very high γ regioselectivity, allowing the method to be applied to the synthesis of 6-oxo-α,β-unsaturated carbonyl compounds.

Rotational barriers of biphenyls having heavy heteroatoms as ortho-substituents: experimental and theoretical determination of steric effects

The free energies of activation for the aryl-aryl rotation of 17 biphenyl derivatives, bearing a heavy heteroatom (S, Se, Te, P, Si, Sn) as ortho substituent, have been measured by variable temperature NMR. These numbers, so called B values, represent a meaningful measure of the steric hindrance exerted by the selected substituents. DFT computations match quite satisfactorily the experimental barriers and the ground state geometries as well (determined, in two cases, by X-ray diffraction). The present values extend the available list of B values and thus provide an enlarged basis for the compilation of the space requirements of standard substituents, based solely on experimental determinations.

Dimethyl arylmalonates from cerium(IV) ammonium nitrate promoted reactions of dimethyl malonate with aromatic compounds in methanol

Abstract Aromatic compounds undergo homolytic malonylation by reaction with cerium(IV) ammonium nitrate and dimethyl malonate in methanol at room temperature.

Optimization of Small-Molecule Inhibitors of Influenza Virus Polymerase: From Thiophene-3-Carboxamide to Polyamido Scaffolds

Influenza virus infections represent a serious concern to public health, being characterized by high morbidity and significant mortality. To date, compounds targeting the viral ion-channel M2 or the viral neuraminidase are the drugs available for treatment of influenza, but the emergence of drug-resistant viral mutants renders the search for novel targets and their possible inhibitors a major priority. Recently, we demonstrated that the viral RNA-dependent RNA polymerase (RdRP) complex can be an optimal target of protein-protein disruption by small molecules, with thiophene-3-carboxamide derivatives emerging as promising candidates for the development of new anti-influenza drugs with broad-spectrum activity. Here, we report a further dissection of the thiophene-3-carboxamide structure. By using a GRID molecular interaction field (MIF)-based scaffold-hopping approach, more potent and nontoxic polyamido derivatives were identified, highlighting a new space in the chemical variability of RdRP inhibitors. Finally, a possible pharmacophoric model highlighting the key features required for RdRP inhibition is proposed.

Enzymatic kinetic resolution of (±)-4-acetoxy[2.2]paracyclophane by Candida cylindracea lipase. An efficient route for the preparation of (+)-R-4-hydroxy- and (+)-S-4-acetoxy[2.2]paracyclophane

Abstract The enzymatic kinetic resolution of (±)-4-acetoxy[2.2]paracyclophane by Candida cylindracea lipase was investigated in water and in a two-phase aqueous organic system. The (+)-(R)-4-hydroxy- and (+)-(S)-4-acetoxy[2.2]-paracyclophanes were isolated in excellent yields and high enantiomeric excesses. The resolution was carried out on multi-gram scale in hexane-water at 40° C.

The biphenyl-monitored effective size of unsaturated functional or fluorinated ortho substituents.

The size of a series of typical substituents has been probed by dynamic NMR measurements of the barriers to aryl-aryl rotation of the corresponding biphenyls. The resulting B values are meaningful because only mono-ortho substituted compounds were investigated and thus the results are not compromised by the non-additivity of multiple steric effects. On the basis of the chosen model system ethynyl and cyano groups were found to be slightly smaller than a phenyl ring. In contrast, vinyl and, in particular, formyl groups proved to be larger than phenyl. The latter difference is due to the loss of conjugation forces at the planar transition state. Alpha-Hydroxyhexafluoroisopropyl is slightly more bulky than tert-butyl. Pentafluorophenyl and trifluoromethoxy exhibit nearly the same effective size as phenyl and methoxy, respectively. Trifluoromethyl is somewhat smaller than isopropyl.

Indole Based Weapons to Fight Antibiotic Resistance: A Structure–Activity Relationship Study

Antibiotic resistance represents a worldwide concern, especially regarding the outbreak of methicillin-resistant Staphylococcus aureus, a common cause for serious skin and soft tissues infections. A major contributor to Staphylococcus aureus antibiotic resistance is the NorA efflux pump, which is able to extrude selected antibacterial drugs and biocides from the membrane, lowering their effective concentrations. Thus, the inhibition of NorA represents a promising and challenging strategy that would allow recycling of substrate antimicrobial agents. Among NorA inhibitors, the indole scaffold proved particularly effective and suitable for further optimization. In this study, some unexplored modifications on the indole scaffold are proposed. In particular, for the first time, substitutions at the C5 and N1 positions have been designed to give 48 compounds, which were synthesized and tested against norA-overexpressing S. aureus. Among them, 4 compounds have NorA IC50 values lower than 5.0 μM proving to be good efflux pump inhibitor (EPI) candidates. In addition, preliminary data on their ADME (absorption, distribution, metabolism, and excretion) profile is reported.

Cerium (IV) ammonium nitrate promoted oxidative cyclization of dimethyl 4-pentenylmalonate

Abstract CAN promoted oxidative cyclization of dimethyl 4-pentenylmalonate has been investigated in MeOH and in AcOH. The product distribution and the regioselectivity of the reaction (5-exo/6-endo ratio) appear to be very sensitive to the reaction conditions as well as the presence and the nature of copper salts, which can also be exploited from the synthetic point of view.