Design, synthesis, docking studies and monoamine oxidase inhibition of a small library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1h)-pyrazoles

New N-acetyl/N-thiocarbamoylpyrazoline derivatives were designed and synthesized in high yields to assess their inhibitory activity and selectivity against human monoamine oxidase A and B. The most important chiral compounds were separated into their single enantiomers and tested. The impact of the substituents at N1, C3 and C5 positions as well the influence of the configuration of the C5 on the biological activity were analyzed. Bulky aromatic groups at C5 were not tolerated. p-Prenyloxyaryl moiety at C3 oriented the selectivity toward the B isoform. The results were also corroborated by molecular modelling studies providing new suggestions for the synthesis of privileged structures to serve as lead compounds for the treatment of mood disorders and neurodegenerative diseases

A new C2-symmetric atropisomeric thiophene-based monomer for inherently chiral electroactive materials: synthesis, HPLC resolution, and absolute configuration assignment

Herein, we report on the synthesis and high-performance liquid chromatography (HPLC) resolution of a new atropisomeric C2-symmetry chiral monomer based on the 3,3′-bithiophene core, which was developed to produce novel, inherently oligomeric chiral electroactive materials. The analytical enantioseparation was optimized using the cellulose-type Chiralpak IB-3 column and a mixture of n-hexane–methanol–dichloromethane 90:5:5 (v/v/v) as the mobile phase. During the scale-up of the enantioseparation analytical conditions to a semipreparative level, remarkable deformations in the HPLC profile, such as peak splitting and plateau zones between enantiomeric peaks, were observed. We demonstrate the effects of sample diluent as they relate to distorted peak profiles, as well as provide experimental solutions to prevent the disturbing phenomenon. The optimized chromatographic conditions were exploited to collect milligram amounts of the enantiopure sample, which was submitted to chiroptical and stereochemical characterization studies

3-(Phenyl-4-oxy)-5-phenyl-4,5-dihydro-(1H)-pyrazole: a fascinating molecular framework to study the enantioseparation ability of the amylose (3,5-dimethylphenylcarbamate) chiral stationary phase. Part I. Structure-enantioselectivity relationships

Chiral stationary phases (CSPs) based on amylose (3,5-dimethylphenylcarbamate) (ADMPC) exhibit awide-range of enantioselectivity in high-performance liquid chromatography (HPLC) and supercriticalfluid chromatography (SFC). Although this class of CSPs has been extensively used, chiral discriminationsat receptorial level, which are useful to develop predictive molecular models, have been rarely reportedin the literature.Herein, we describe the results obtained in the enantioselective HPLC of a set of six C5-chiral 4,5-dihydro-(1H)-pyrazole derivatives on the ADMPC-based Chiralpak AD-3 CSP (CSP) under normal-phaseand polar organic conditions. Using pure methanol as a mobile phase the exceptional enantioseparationfactor value of 50 at 25◦C was found for one of the investigated analytes. To the best of our knowledge, theenantiomeric bias represents the most outstanding enantioseparation ever recorded on ADMPC-basedCSPs.Systematic variations in chemical groups in specific positions of the 3-(phenyl-4-oxy)-5-phenyl-4,5-dihydro-(1H)-pyrazole molecular framework resulted in peculiar changes in retention andenantioselectivity. A careful analysis of the chromatographic data permitted to advance some hypothesesconcerning the role played by the individual chemical groups in determining the exceptional enantiosep-aration.In particular, under methanol-rich mode, the prenyl moiety of the second eluted enantiomer of thebetter resolved analyte was recognized as a critical structural element to establish direct and favorablesolvophobic interactions with apolar portions of selector

TetraPh-Tol-BITIOPO: a new atropisomeric 3,3’-bithiophene based phosphine oxide as organocatalyst in Lewis Base-catalyzed Lewis Acid mediated reactions

A new chiral phosphine oxide based on 3,3’-bithiophene scaffold (tetraPh-Tol-BITIOPO) was synthesized, fully characterized and separated into antipodes through chiral HPLC. This new compound was successfully employed as organocatalyst in Lewis base-catalyzed Lewis acid mediated reactions involving trichlorosilyl compounds. The new atropisomeric catalyst was able to promote the allylation of aldehydes with allyltrichlorosilane in up to 98% yield and up to 96% enantiomeric excess (ee), and the direct aldol reaction to afford β-hydroxy ketones and β-hydroxy thioesters, with good chemical yields and modest stereochemical efficiency. Computational studies helped to elucidate and to rationalize the stereochemical outcome of the reactions catalyzed by TetraPh-Tol-BITIOPO, that was found to favour the formation of the isomer with the opposite absolute configuration in comparison with the products obtained with the previously reported 3,3’-bithiophene-based catalyst

In Situ Electrochemical Investigations of Inherently Chiral 2,2′-Biindole Architectures with Oligothiophene Terminals

AbstractThe synthesis and characterization of three new inherently chiral N,N′‐dipropyl‐3,3′‐diheteroaryl‐2,2′‐biindole monomers, nicknamed Ind2T4, Ind2T6 and Ind2Ph2T4, which differ in the number of thiophenes as terminals, are reported. In addition to a full monomer characterization, stable electroactive oligomeric films were obtained by electro‐oxidation upon cycling to potentials which activate the thiophene terminals. Cyclic voltammetry, UV‐Vis‐NIR spectroelectrochemistry and in situ conductance measurements show that oligomeric films of Ind2T6 present the best stability and electrochromic switching performance. Enantioselective tests with a chiral ferrocene amine clearly show the potential as chiral selectors for analytical and sensing purposes

An "inherently chiral" 1,1′-bibenzimidazolium additive for enantioselective voltammetry in ionic liquid media

A dialkyl-1,1′-bibenzimidazolium salt, consisting of an atropisomeric dication (i.e. featuring a stereogenic axis and thus "inherently chiral") and an achiral counteranion, is employed as a chiral additive in three commercial ionic liquids, providing successful enantiodiscrimination in voltammetry experiments on screen-printed electrodes (SPEs) with the enantiomers of N,N′-dimethyl-1-ferrocenyl-ethylamine as model chiral probes. Significant differences in redox potentials are observed for the probe enantiomers despite the low concentration (0.01 M) of the chiral additive. The nature of the achiral ionic liquid in which the additive is employed significantly affects the peak potentials and potential differences, but does not alter the enantiomer sequence. Keywords: Chiral electrochemistry and electroanalysis, Ionic liquids, Chiral additives, Inherent chirality, Enantiorecognitio

Palynostratigraphy of the Permian Faraghan Formation in the Zagros Basin, southern Iran

A detailed microfloristic study was conducted in the Faraghan Formation in nine boreholes drilled by the National Iranian Oil Company (NIOC) and in four outcrops in the Zagros Basin. The Faraghan Formation, widely distributed in the Zagros area, generally consists of shale intercalated with sandstone and pebble conglomerate, with thin carbonate intercalations near the top. Due to the lack of significant fossils, the age of this rock unit has been strongly debated in the Iranian literature and uncertainly attributed to the Pennsylvanian or Cisuralian. In this study, the age of the Faraghan Formation was reviewed in light of new biostratigraphic advances in the Arabian Peninsula. The assemblage is characterized by an abundance of monosaccate pollen such as Florinites? balmei, Caheniasaccites spp., Plicatipollenites spp., Potonieisporites spp. and Striomonosaccites spp., and bisaccate pollen such as Alisporites spp., Corisaccites alutas, Distriatites insolitus, Hamiapollenites spp. and Striatopodocarpites spp.. The assemblage also contains polyplicate pollen such as Vittatina spp.. Spores such as Indotriradites mundus and Thymospora opaqua are also present. The stratigraphic ranges of the taxa allow reference to the biozone schemes for Oman and assignment of the Faraghan Formation to the Guadalupian

Assessing thermal maturity through a multi-proxy approach: a case study from the Permian Faraghan Formation (Zagros Basin, Southwest Iran)

This study focuses on the thermal maturity of Permian deposits from the Zagros Basin, Southwest Iran, employing both optical methods (Thermal Alteration Index, Palynomorph Darkness Index, Vitrinite Reflectance, UV Fluorescence) and geochemical analyses of organic matter (Rock Eval Pyrolysis and MicroRaman spectroscopy) applied to the Faraghan Formation along two investigated Darreh Yas and Kuh e Faraghan surface sections. Furthermore, an integrated palynofacies and lithofacies analysis was carried out in order to integrate the few studies on the depositional environment. The Faraghan Formation, which is widely distributed in the Zagros area, generally consists of shale intercalated with sandstones and pebble conglomerates in the lower part, followed by a succession of sandstone, siltstone and shaly intercalations and with carbonate levels at the top. The integrated palynofacies and lithofacies data confirm a coastal depositional setting evolving upwards to a shallow marine carbonate environment upwards. Rock Eval Pyrolysis and Vitrinite Reflectance analysis showed that the organic matter from samples of the Darreh Yas and Kuh e Faraghan sections fall in the mature to postmature range with respect to the oil to gas generation window, restricting the thermal maturity range proposed by previous authors. Similar results were obtained with MicroRaman spectroscopy and optical analysis such as Thermal Alteration Index and UV Fluorescence. Palynomorph Darkness Index values were compared with Rock Eval Pyrolysis and vitrinite reflectance values and discussed for the first time in the late stage of oil generation.This research was funded by PRIN (2017RX9XXXY-CIRILLI), by Fondo Ricerca di Base Department of Physics and Geology, University of Perugia (SPIRICBAS2018-SPINA), by the project “Paleontological Studies and Biozonation of Paleozoic Sediments in Central Iran and Zagros Basins” (coordinator R. Rettori) and MIUR grants-SORCI to PhD School of Science and Technology for Physics and Geology (XXXIV Cycle), University of Perugia; Project “Paleontological Studies and Biozonation of Paleozoic Sediments in Central Iran and Zagros Basins” (RETTORI).info:eu-repo/semantics/publishedVersio

THE PRATI DI STUORES/STUORES WIESEN SECTION (DOLOMITES, ITALY): A CANDIDATE GLOBAL STRATOTYPE SECTION AND POINT FOR THE BASE OF THE CARNIAN STAGE

The Prati di Stuores/Stuores Wiesen section (Dolomites, Italy) is proposed as a candidate Global Stratotype Section and Point for the base of the Carnian Stage. In addition to being a famous, richly fossiliferous locality, it includes the type-section of the Cordevolian substage. The section is located near Pralongià, along the southern slope of the crest separating the Badia/Abtei and Cordevole valleys. Below the levels with Trachyceras aon, the section contains a rich ammonoid fauna that chacterizes the lower part of the Regoledanus Subzone and subsequently records the first appearances of the mid-high latitude genus Daxatina (Daxatina sp., D. cf. canadensis) and of traditional Trachyceras with species different from T. aon. Moreover, the Daxatina cf. canadensis Subzone is recognised above the Regoledanus Subzone. Very rare conodonts of the Budurovignatus group and species of Gladigondolella from the diebeli Assemblage Zone occur. Gondolella polygnatyformis, already known from the Aon Subzone, is absent. Palynomorphs, foraminifers, gastropods, bivalves, brachiopods, microcrinoids and holothurian sclerites were studied. Variations in frequency and taxonomic diversity of these faunas suggest anaerobic-disaerobic bottom conditions for the lower-middle part of the section (0-105 m), followed by a more stable oxygen content in the upper portion. Magnetostratigraphy showed four intervals with normal polarity and three intervals with reversed polarity. The Daxatina cf. canadensis Subzone falls close to the normal polarity interval S2n. The present study proposes the FAD of the cosmopolitan genus Daxatina as a marker of the base of the Carnian Stage, placing it at a lower stratigraphic level than previously indicated in the Stuores area. The Prati di Stuores section is proposed as GSSP of the Ladinian-Carnian boundary.&nbsp

Chiral indolylarylsulfone non-nucleoside reverse transcriptase inhibitors as new potent and broad spectrum anti-HIV-1 agents

We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The new IASs 8–37 showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L, and K103N–Y181C HIV-1 strains. Six racemic mixtures, 8, 23–25, 31, and 33, were separated at semipreparative level into their pure enantiomers. The (R)-8 enantiomer bearing the chiral (α-methylbenzyl) was superior to the (S)-counterpart. IAS derivatives bearing the (S) alanine unit, (S)-23, (S,R)-25, (S)-31, and (S)-33, were remarkably more potent than the corresponding (R)-enantiomers. Compound 23 protected hippocampal neuronal cells from the excitotoxic insult, while efavirenz (EFV) did not contrast the neurotoxic effect of glutamate. The present results highlight the chiral IASs as new NNRTIs with improved resistance profile against the mutant HIV-1 strains and reduced neurotoxic effects