Synthesis and stereochemistry of 2-arylperhydrocyclopenta[b]pyridin-1-ols, 8-azaestrone fragments

Different stereoisomers of 2-arylperhydrocyclopenta[b]pyridin-1-ols, which form structural motifs of 8-azaestrone, were prepared via reductive cyclization from mono-oximes derived from 1,5-diketones, by using sodium borohydride and acetic acid in THF at reflux.     

New reagent for the introduction of Boc protecting group to amines: Boc-OASUD

A new reagent, tert-butyl (2,4-dioxo-3-azaspiro [5,5] undecan-3-yl) carbonate (Boc-OASUD) for the preparation of N-Boc-amino acids is described. The Boc-OASUD reacts with amino acids and their esters at room temperature in the presence of a base and gives N-Boc-amino acids and their esters in good yields and purity. Introduction of the Boc group takes place without racemization. The Boc-OASUD, being a solid and more stable, is a better alternative to di-tert-butyl dicarbonate which is low melting and has to be dispensed in plastic containers than glass because of its poor stability.     

Quantitative estimation of riluzole in human plasma by LC-ESI-MS/MS and its application to a bioequivalence study

A novel simple, sensitive, selective, and rapid high-performance liquid chromatography coupled with tandem mass spectrometry method was developed and validated for quantification of riluzole in human plasma. The chromatography was performed by using a Zorbax-SB-C18 (4.6 × 75 mm, 3.5 μm) column , isocratic mobile phase 0.1% formic acid/acetonitrile (10:90 v/v), and an isotope-labeled internal standard (IS), [¹³C,¹⁵N₂]riluzole. The extraction of drug and internal standard was performed by liquid–liquid extraction and analyzed by MS in the multiple reaction monitoring (MRM) mode using the respective [M+H]⁺ ions, m/z 235.0/165.9 for riluzole and m/z 238.1/169.0 for the IS. The calibration curve was linear over the concentration range 0.5–500.0 ng/ml for riluzole in human plasma. The limit of quantification (LOQ) was demonstrated at 0.5 ng/ml. The within-batch and between-batch precision were 0.6–2.3% and 1.4–5.7%, and accuracy was 97.1–101.1% and 98.8–101.2% for riluzole respectively. Drug and IS were eluted within 3.0 min. The validated method was successfully applied in a bioequivalence study of riluzole in human plasma.     

Improved lower bounds on the total variation distance for the Poisson approximation

New lower bounds on the total variation distance between the distribution of a sum of independent Bernoulli random variables and the Poisson random variable (with the same mean) are derived via the Chen–Stein method. The new bounds rely on a non-trivial modification of the analysis by Barbour and Hall (1984) which surprisingly gives a significant improvement. A use of the new lower bounds is addressed.     

Optimal control of self-organized dynamics in cellular signal transduction

We demonstrate how model-based optimal control can be exploited in biological and biochemical modelling applications in several ways. In the first part, we apply optimal control to a detailed kinetic model of a glycolysis oscillator, which plays a central role in immune cells, in order to analyse potential regulatory mechanisms in the dynamics of associated signalling pathways. We demonstrate that the formulation of inverse problems with the aim to determine specific time-dependent input stimuli can provide important insight into dynamic regulations of self-organized cellular signal transduction. In the second part, we present an optimal control study aimed at target-oriented manipulation of a biological rhythm, an internal clock mechanism related to the circadian oscillator. This oscillator is responsible for the approximate endogenous 24 h (latin: circa dies) day-night rhythm in many organisms. On the basis of a kinetic model for the fruit fly Drosophila, we compute switching light stimuli via mixed-integer optimal control that annihilate the oscillations for a fixed time interval. Insight gained from such model-based specific manipulation may be promising in biomedical applications.     

Freeze-drying synthesis and characterisation of Na composites of ZnO,TiO<Subscript>2</Subscript> and ZnTiO<Subscript>3</Subscript> semiconductor oxides

The freeze-drying method of metal oxides synthesis has a number of advantages such as high homogeneity, varying porous structures, morphologies and uniform particle size distribution, etc. Because of these advantages, the binary metal oxides ZnO, TiO₂ and ternary metal oxide ZnTiO₃ were synthesised by the freeze-drying method. The synthesised materials were characterised by X-ray diffraction (XRD), Fourier transform-infra red spectroscopy (FT-IR), UV-VIS spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDAX). The as-synthesised metal oxides were calcined at different temperatures to study the phase evolution and morphological changes. The crystalline cubic-phase ZnTiO₃ (a = 8.3948 Å) was obtained on calcination of the precursor at 600°C, and decomposed to the cubic phase Zn₂TiO₄ (a = 8.4580 Å) and rutile TiO₂ (a = 4.5955 Å and c = 2.9593 Å) at 1000°C. The band gap of ZnO (3.28?3.10 eV), TiO₂ (3.37?2.97 eV) and ZnTiO₃ (3.92?3.80 eV) calculated using Tauc’s relation was found to vary inversely with calcination temperature and phase transition.     

Morita–Baylis–Hillman (MBH) Reaction Derived Nitroallylic Alcohols,Acetates and Amines as Synthons in Organocatalysis and Heterocycle Synthesis

The Morita–Baylis–Hillman (MBH) reaction is one of the most useful and efficient protocols for constructing new carbon–carbon bonds between an activated olefin and electrophiles in the presence of a tertiary amine/phosphine. Herein, we present the use of MBH alcohols, which are obtained from the reaction of nitrostyrenes with aldehydes, as well as acetates and amines derived thereof in several organocatalytic transformations. Densely functionalised MBH adducts can also be used to synthesise substituted heteroaromatic compounds, such as furan, pyrrole, pyrazole and imidazole derivatives.     

Expeditious,Nano-BF3 · SiO2-Catalyzed Michaelis–Arbuzov Reaction in an Ionic Liquid: Synthesis of Privileged Aryl/Heterocyclic Phosphonates

An expeditious, simple, and green method was developed for the synthesis of privileged aryl/heterocyclicphosphonates, 8(a–c) to 13(a–c) through Michaelis–Arbuzov reaction of aryl/heterocyclic halides (Br), 1–6, and trialkylphosphites, 7(a–c), in room-temperature ionic liquid [bbim]Br using heterogeneous Lewis catalyst, nano-silica-supported boron trifluoride (BF₃-SiO₂). The advantages of this protocol are simplicity, good yield of the products, less reaction time (20–38 min), mild reaction conditions, easy workup, and reusability of the catalyst and ionic liquid. It is demonstrated that nano-BF₃-SiO₂ is a recoverable and easy accessible catalyst for the formation of C(sp²)-P bond in an ionic liquid.     

Pyrrolidine-linker-camphor assembly: bifunctional organocatalysts for efficient Michael addition of cyclohexanone to nitroolefins under neat conditions

A simple and convenient strategy was developed to synthesize a new class of pyrrolidinyl-camphor based bifunctional organocatalysts possessing varying functional linkers. Catalytic screening of these camphor-pyrrolidine linked derivatives for asymmetric Michael reaction of cyclohexanone with β-nitrostyrene was carried out. Various aryl- and heteroaryl-nitroolefins, ketones as well as aldehydes gave the corresponding Michael adducts in high chemical yields (up to 95%) and exceptionally high diastereo-(syn/anti up to 99:1) and enantioselectivity (up to 95%) using catalyst 6 under solvent-free conditions.