New Insights into Dietary Pterostilbene: Sources,Metabolism, and Health Promotion Effects

Pterostilbene (PTS), a compound most abundantly found in blueberries, is a natural analog of resveratrol. Several plant species, such as peanuts and grapes, produce PTS. While resveratrol has been extensively studied for its antioxidant properties, recent evidence also points out the diverse therapeutic potential of PTS. Several studies have identified the robust pharmacodynamic features of PTS, including better intestinal absorption and elevated hepatic stability than resveratrol. Indeed, due to its higher bioavailability paired with reduced toxicity compared to other stilbenes, PTS has become an attractive drug candidate for the treatment of several disease conditions, including diabetes, cancer, cardiovascular disease, neurodegenerative disorders, and aging. This review article provides an extensive summary of the nutraceutical potential of PTS in various disease conditions while discussing the crucial mechanistic pathways implicated. In particular, we share insights from our studies about the Nrf2-mediated effect of PTS in diabetes and associated complications. Moreover, we elucidate the important sources of PTS and discuss in detail its pharmacokinetics and the range of formulations and routes of administration used across experimental studies and human clinical trials. Furthermore, this review also summarizes the strategies successfully used to improve dietary availability and the bio-accessibility of PTS.     

Ligand-Enabled Palladium-Catalyzed Through-Space C−H Bond Activation via a Carbopalladation/1,4-Pd Migration/C−H Functionalization Sequence

We report, herein, a palladium-catalyzed cascade comprising carbopalladation, 1,4-Pd-migration and C(sp²)−C(sp²) bond formation to construct a variety of bis-heterocyclic frameworks in a single operational step. The methodology provides a direct approach to introduce an oxadiazole core at a remote location without any functional group obligation, with moderate to good yields.     

Synthesis of trans -N-2-aryl(heteryl)ethenamidines

2-Amino-2-arylethylamides1 carrying electron-donating substituents in thepara position are transformed by hot POC1₃ to the the title compounds2, presumably via iminochlorides 7 and imidazolium derivatives8. Amides lacking this para-substituent give rise to chloroamidines11 under these conditions.m-Methoxyphenethylamide1t and POCl₃ form, besides11f, an isoquinoline derivative3. The involvement of an imidazolium compound8 in the formation of ethenamidines has been verified by the synthesis of2a from10. Reaction of amide1w with PCl₅ in the cold leads to, besides the chloroamidine11c, thecis-ethenamidine12 which equilibrates with thetrans-isomer2o in hot toluene. Thienylethyl urea13 converted by hot POCl₃ to the imidazoline16, while phenylpropylamide17 forms only the iminochloride18a. Contribution No. 752 from Research Centre     

Highly diastereoselective synthesis of new chromenylaminoanthraquinones through a one-pot, three-component hetero Diels–Alder reaction

A new, efficient, and diastereoselective one-pot synthesis of cis-fused pyrano and furano chromenylaminoanthraquinones through hetero Diels–Alder reaction of 1-aminoanthraquinone and salicylaldehydes with electron-rich alkenes such as 3,4-dihydro-2H-pyran, 2,3-dihydrofuran, and ethyl vinyl ether under mild conditions is reported.     

Multiple hydrogen bonding induced self-assembly: transformation from nanofibrils to nanosphere with aromatic oligoamide incorporated polyethylene glycol

Aromatic oligoamides bearing six potential hydrogen-bonding sites were designed and synthesized. Functionalized with two polyethylene glycol (M_w?=?2000), this aromatic oligoamide could self-assemble via hydrogen bonds to form nanofibrils in nonpolar solvents as a result of aggregation. The resulting aggregates were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM) and dynamic light scattering (DLS). Upon adding another aromatic oligoamide containing complementary hydrogen bond donors and acceptors, transformation from nanofibrils to nanosphere was observed due to formation of hydrogen-bonded duplex. The nanospherical micelle was corroborated by SEM, transmission electron microscopy (TEM) and AFM tests. The results achieved here demonstrate an alternative route to effect supramolecular structures via multiple hydrogen bonding-induced self-assembly process.     

<Emphasis Type="Italic">In-silico</Emphasis> Screening using Flexible Ligand Binding Pockets: A Molecular Dynamics-based Approach

Summary In-silico screening of flexible ligands against flexible ligand binding pockets (LBP) is an emerging approach in structure-based drug discovery. Here, we describe a molecular dynamics (MD) based docking approach to investigate the influence on the high-throughput in-silico screening of small molecules against flexible ligand binding pockets. In our approach, an ensemble of 51 energetically favorable structures of the LBP of human estrogen receptor α (hERα) were collected from 3 ns MD simulations. In-silico screening of 3500 endocrine disrupting compounds against these flexible ligand binding pockets resulted in thousands of ER–ligand complexes of which 582 compounds were unique. Detailed analysis of MD generated structures showed that only 17 of the LBP residues significantly contribute to the overall binding pocket flexibility. Using the flexible LBP conformations generated, we have identified 32 compounds that bind better to the flexible ligand-binding pockets compared to the crystal structure. These compounds, though chemically divergent, are structurally similar to the natural hormone. Our MD-based approach in conjunction with grid–based distributed computing could be applied routinely for in-silico screening of large databases against any given target.     

Quantenmechanische Untersuchung absoluter Ramanintensitäten

Zusammenfassung Ausgehend vom Deltafunktionspotentialmodell wurde die absolute Intensität einer Ramanlinie, die dem Quadrat der molekularen Polarisierbarkeit proportional ist, bestimmt. Auf Grund des Deltafunktionspotentialmodells ergibt sich eine Abhängigkeit der Komponente der Polarisierbarkeit in der Bindungsrichtung vonR ⁴. Wir leiteten aus dem Deltafunktionspotentialmodell einen Ausdruck für die Ableitung der mittleren molekularen Polarisierbarkeit nach der Entfernung der Kerne aus der Gleichgewichtskonfiguration ab, der für viele zweiatomige Moleküle und für die symmetrischen Streckschwingungen vieler mehratomiger Moleküle und Ionen im elektronischen Grundzustand zutrifft. Die berechneten Werte für die Ableitung der Polarisierbarkeit stimmen meist gut mit den aus den experimentell bestimmten Ramanintensitäten erhaltenen Werten überein. Mit Hilfe des Deltafunktionspotentialmodells errechneten wir aus den experimentell bestimmten Ableitungen der Polarisierbarkeit Bindungsordnungen für verschiedene ionische Systeme und erörterten die Ergebnisse im Hinblick auf die Beiträge der - und -Elektronen zu den Ableitungen der Polarisierbarkeit von Mehrfachbindungen.

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Quantum mechanical studies of absolute raman intensities (application to symmetrical stretching modes in some molecules and ions)

Absolute intensity of a Raman line which is proportional to the square of the derivative of molecular polarizability has been determined from the delta-function potential model yielding theR ⁴-dependence of the bond parallel component of the polarizability. The delta-function potential model has been used to derive the expression for the derivative of the mean molecular polarizability with respect to a change in the internuclear distance at the equilibrium configuration for many diatomic molecules, and for the symmetrical stretching modes of many polyatomic molecules and ions in the ground electronic state. The computed polarizability derivatives are in good agreement with most of the experimental ones derived from Raman intensities. Bond orders have been computed from the experimental polarizability derivatives for various ionic systems through the use of the delta-function potential model, and the results have been discussed in relation to the contributions of the and electrons to the polarizability derivatives of multiple bonds.

     

P(i-BuNCH2CH2)3N: an effective ligand in the palladium-catalyzed amination of aryl bromides and iodides

It is shown that the bicyclic triaminophosphine P(i-BuNCH2CH2)3N serves as an effective ligand for the palladium-catalyzed amination of a wide array of aryl bromides and iodides. Other bicyclic or acyclic triaminophosphines, even those of similar basicity and/or bulk, were inferior.