Bioisosteric Exchange of C ‐Chloro and Methyl Substituents: Synthesis and Initial Biological Studies of Atpenin A5 Analogues

Asymmetric synthesis and initial biological studies of two analogues of a naturally occurring chlorinated antifungal agent, atpenin A5, are described. These analogues were selected on the basis of Cl→CH₃ or H₃C→Cl exchanges in the side‐chain of atpenin A5. The interchange of chloro and methyl substituents led to complex II inhibitors with equal IC₅₀ values. This suggests that Cl?Me bioisosteric exchange can be realized in aliphatic settings.     

Improved high-performance liquid chromatography-diode array detection method for the determination of phenolic compounds in leaves and peels from different apple varieties

Hydroxycinnamic acids derivatives, monomeric and oligomeric flavan-3-ols, flavonols, and dihydrocalcones are four of the major polyphenolic groups found in apples leaves and peels. A simple extraction with minimal pre-treatment and a high-performance liquid chromatography-diode array detection determination are optimized and validated, in order to identify and quantitate the polyphenolic profile of leaves and peels of four apples varieties (Gala, Topaz, Golden Delicious, and Florina). The improved chromatographic method has led to better separation of some known polyphenols in a single course, and diode-array detection has been used for the previsional identification of some polyphenolic compounds not available as standards. Because the mobile phase and the chromatographic column are compatible with a mass spectrometer, this method could investigate the unknown flavanols, flavonols, hydrocinnamic acid derivatives, and chalcone-related compounds found in apple leaves and peel extracts analyzed.     

Finding the First Potential Inhibitors of Shikimate Kinase from Methicillin Resistant Staphylococcus aureus through Computer-Assisted Drug Design

Methicillin-resistant Staphylococcus aureus (MRSA) is an important threat as it causes serious hospital and community acquired infections with deathly outcomes oftentimes, therefore, development of new treatments against this bacterium is a priority. Shikimate kinase, an enzyme in the shikimate pathway, is considered a good target for developing antimicrobial drugs; this is given because of its pathway, which is essential in bacteria whereas it is absent in mammals. In this work, a computer-assisted drug design strategy was used to report the first potentials inhibitors for Shikimate kinase from methicillin-resistant Staphylococcus aureus (SaSK), employing approximately 5 million compounds from ZINC15 database. Diverse filtering criteria, related to druglike characteristics and virtual docking screening in the shikimate binding site, were performed to select structurally diverse potential inhibitors from SaSK. Molecular dynamics simulations were performed to elucidate the dynamic behavior of each SaSK–ligand complex. The potential inhibitors formed important interactions with residues that are crucial for enzyme catalysis, such as Asp37, Arg61, Gly82, and Arg138. Therefore, the compounds reported provide valuable information and can be seen as the first step toward developing SaSK inhibitors in the search of new drugs against MRSA.     

Measurement and analysis of rolling tire vibrations

This paper presents the measurement and analysis of rolling tire vibrations due to road impact excitations, such as from cobbled roads, junctions between concrete road surface plates, railroad crossings. Vibrations of the tire surface due to road impact excitations cause noise radiation in the frequency band typically below 500 Hz. Tire vibration measurements with a laser Doppler vibrometer are performed on a test set-up based on a tire-on-tire principle which allows highly repetitive and controllable impact excitation tests under various realistic operating conditions. The influence on the measured velocity of random noise, cross sensitivity and alignment errors is discussed. An operational modal analysis technique is applied on sequential vibration measurements to characterise the dynamic behaviour of the rolling tire. Comparison between the operational modal parameters of the rolling tire and the modal parameters of the non-rolling tire allows an assessment of the changes in dynamic behaviour due to rolling.     

Simulation of vibrational dephasing of I(2) in solid Kr using the semiclassical Liouville method

In this paper, we present simulations of the decay of quantum coherence between vibrational states of I(2) in its ground (X) electronic state embedded in a cryogenic Kr matrix. We employ a numerical method based on the semiclassical limit of the quantum Liouville equation, which allows the simulation of the evolution and decay of quantum vibrational coherence using classical trajectories and ensemble averaging. The vibrational level-dependent interaction of the I(2)(X) oscillator with the rare-gas environment is modeled using a recently developed method for constructing state-dependent many-body potentials for quantum vibrations in a many-body classical environment [J. M. Riga, E. Fredj, and C. C. Martens, J. Chem. Phys. 122, 174107 (2005)]. The vibrational dephasing rates gamma(0n) for coherences prepared between the ground vibrational state mid R:0 and excited vibrational state mid R:n are calculated as a function of n and lattice temperature T. Excellent agreement with recent experiments performed by Karavitis et al. [Phys. Chem. Chem. Phys. 7, 791 (2005)] is obtained.     

Synthesis of (+/-)-strychnofoline via a highly convergent selective annulation reaction

Studies aimed at preparing (+/-)-strychnofoline by total synthesis are detailed. The route described makes use of a recently developed MgI(2)-mediated ring-expansion reaction of spiro[cyclopropan-1,3'-oxindole] with a cyclic disubstituted aldimine. The ring-expansion product was formed as a single diastereoisomer in 55 % yield, possessing the same stereochemical pattern found in strychnofoline. In addition, our synthetic effort has led to the development of new reaction methodology to access 3,4-disubstituted cyclic aldimines.     

Total synthesis and stereochemical reassignment of (±)-indoxamycin b

Revised version: The first total synthesis of indoxamycin?B leads to a stereochemical reassignment of the natural product. The synthetic route features an efficient carboannulation sequence to rapidly access the dihydroindenone system. Moreover, a series of Au(I) -catalyzed transformations served in the construction of the sterically congested core framework.