Bio‐Inspired Formal Synthesis of Hirsutellones A–C Featuring an Electrophilic Cyclization Triggered by Remote Lewis Acid‐Activation

A bio‐inspired strategy was used to complete the formal synthesis of the antitubercular hirsutellone B and congeners A and C, through construction of its decahydrofluorene core from a linear polyene strand activated at both ends by a silyl enol ether and an allyl acetate. Our synthesis features a key electrophilic cyclization, starting with the remote activation (by [Yb(OTf)₃] or BF₃ ? OEt₂) of the allyl acetate and stereoselectively affording the C ring. This was followed by an intramolecular Diels–Alder reaction to get the tricyclic core of the natural product. The stereoselective reduction of the resulting ketone towards the formal intermediate was critical to the success of this strategy.     

A green route to enantioenriched (S)-arylalkyl carbinols by deracemization via combined lipase alkaline-hydrolysis/Mitsunobu esterification

Herein we report results of the chemoenzymatic deracemization of a range of secondary benzylic acetates 1a–9a via a sequence of hydrolysis with CAL-B lipase in non-conventional media, combined with esterification of the recovered alcohol according to the Mitsunobu protocol following an enzymatic kinetic resolution (KR). The KR of racemic acetates 1a–9a via an enzymatic hydrolysis, with CAL-B lipase and Na₂CO₃, in non-aqueous media was optimized and gave high selectivities (E ? 200) at good conversions (C >49%) for all of the substrates studied. This method competes well with the traditional one performed in a phosphate buffer solution. The deracemization using Mitsunobu inversion gave the (S)-acetates in moderate to excellent enantiomeric excess 75% < ee < 99%, in acceptable isolated yields 70% < yield < 89%, and with some variations according to the acetate structure.     

Electronic structure and spectroscopic properties of 6‐aminophenanthridine and its derivatives: Insights from density functional theory

6‐Aminophenanthridine (6AP) and its derivatives show important biological activities as antiprion compounds and inhibitors of the protein folding activity of the ribosome. Both of these activities depend on the RNA binding property of these compounds, which has been recently characterized by fluorescence spectroscopy. Hence, fundamental insights into the photophysical properties of 6AP compounds are highly important to understand their biological activities. In this work, we have calculated electronic structures and optical properties of 6AP and its three derivatives 6AP8CF₃, 6AP8Cl, and 6APi by density functional theory (DFT) and time‐dependent density functional theory (TDDFT). Our calculated spectra show a good agreement with the experimental absorption and fluorescence spectra, and thus, provide deep insights into the optical properties of the compounds. Furthermore, comparing the results obtained with four different hybrid functionals, we demonstrate that the accuracy of the functionals varies in the order B3LYP > PBE0 > M062X > M06HF. © 2015 Wiley Periodicals, Inc.     

Analysis of polarization mode dispersion fluctuations in single mode fibres due to temperature

We have studied the effect of temperature on the birefringence and polarization mode dispersion PMD in standard single mode fibre (SSMF) with elliptical core cross section by using numerical computations. On the basis of simulation we have concluded that PMD fluctuates more rapidly than the stress-induced birefringence. In addition, DGD is inversely proportional to temperature.     

Competitive adsorption of anionic dyes onto DMOA modified MCM-41

Research on Chemical Intermediates - The single and binary adsorption of two anionic dyes Acid Yellow 17 (AY17) and Naphtol Green B (NGB) onto N–N–Dimethyl-n-octylamine (DMOA) modified...     

In vivo oral insulin delivery via covalent organic frameworks

With diabetes being the 7th leading cause of death worldwide, overcoming issues limiting the oral administration of insulin is of global significance. The development of imine-linked-covalent organic framework (nCOF) nanoparticles for oral insulin delivery to overcome these delivery barriers is herein reported. A gastro-resistant nCOF was prepared from layered nanosheets with insulin loaded between the nanosheet layers. The insulin-loaded nCOF exhibited insulin protection in digestive fluids in vitro as well as glucose-responsive release, and this hyperglycemia-induced release was confirmed in vivo in diabetic rats without noticeable toxic effects. This is strong evidence that nCOF-based oral insulin delivery systems could replace traditional subcutaneous injections easing insulin therapy.

We report the successful use of a gastro-resistant covalent organic framework for in vivo oral delivery of insulin.     

Computational studies of 1:2 complex between retinol propionate and β cyclodextrin

[M05-2X/6-31G*:PM3MM] and [B3LYP/6-31G*:PM3] ONIOM2 methods have been used to investigate the vitamin A propionate/β cyclodextrin complex with 1:2 stoichiometry. Both methods give almost the same lowest energy minimum. The minimum energy structure of the complex is found in good agreement with experimental data. In this configuration, the major structure of propionate of vitamin A (PVA) is embedded inside the two cavities of βCD while the propionate group is kept outside. However, the three methyl groups of PVA are positioned in the free space between both βCD molecules. The driving forces for complexation are dominated by Van der Waals interactions between PVA and the βCD molecules assisted with multiple hydrogen bond interactions between the two cyclodextrin molecules. These interactions were investigated using the natural bond orbital approach.     

Natural product extracts of the Canadian prairie plant,Thermopsis rhombifolia,have anti-cancer activity in phenotypic cell-based assays

Many plant species within the terrestrial ecological zones of Canada have not yet been investigated for anti-cancer activity. We examined the scientific literature describing the endemic flora from the prairie ecological zone and selected the species, Thermopsis rhombifolia, locally known as the buffalo bean, for investigation of its anti-cancer potential. We tested it in cell-based assays using phenotypic screens that feature some of the hallmarks of cancer. An ethanolic extract prepared from T. rhombifolia was cytotoxic to HT-29 (colon) and SH-SY5Y (brain) cancer cell lines, and showed little cytotoxicity to a normal human cell line (WI-38). In phenotypic assays, we identified activities in the extracts that target cell death, cell cycle and cell adhesion. These data highlight the anti-cancer potential of previously untested plants found in northern ecological zones and the feasibility of using pertinent phenotypic assays to examine the anti-cancer potential of natural product extracts.     

Nigericin and grisorixin methyl ester from the Algerian soil-living Streptomyces youssoufiensis SF10 strain: a computational study on their epimeric structures and evaluation of glioblastoma stem cells growth inhibition

The present work describes the metabolites produced by a strain identified as Streptomyces youssoufiensis, whose secondary metabolites profile has not been studied so far. The crude ethyl acetate extract was analyzed by high performance liquid chromatography-electrospray ionization mass spectrometry, leading to the detection of the ionophoric polyethers nigericin, epinigericin, abierixin and the newly isolated grisorixin methyl ester. The presence of epimeric forms of nigericin/epinigericin and grisorixin/epigrisorixin has spurred density functional theory computational calculations. This analysis was able to provide the relative stability of the most favored epimers, setting the basis for general structural considerations applicable to several other polyethers. Both nigericin sodium salt and grisorixin methyl ester showed to affect glioblastoma stem cells proliferation in a dose-dependent manner, with a higher activity for the more lipophilic grisorixin methyl ester (GI₅₀ values of 3.85 and 3.05 μM for VIPI and COMI human glioblastoma stem cells, respectively).