A Facile Synthesis of Raltegravir Potassium—An HIV Integrase Inhibitor

A facile, cost‐effective, and commercially viable synthesis of Raltegravir Potassium ( 1 ) has been developed from 2‐(1‐amino‐1‐methyl‐ethyl)‐N‐[(4‐fluorophenyl)methyl]‐1,6‐dihydro‐5‐hydroxy‐1‐methyl‐6‐oxo‐4‐pyrimidinecarboxamide ( 9 ) with high purity and in good yields. In addition, a new approach for the synthesis of key amine intermediate ( 9 ) of Raltegravir Potassium ( 1 ) from commercially available 2‐amino‐2‐methylpropanenitrile hydrochloride ( 2 ) is also described. The key features of the synthesis are fewer synthetic steps, employing the inexpensive reagents and eco‐friendly.     

An Efficient Oxidative Difunctionalisation of 2-Amino-2H-chromene and Antimicrobial Activity of the Synthesized Tetrahydrochromene Derivatives

A novel series of 3-amino-2,2-dialcoxy-7,7-dimethyl-5-oxo-4-phenyl-3,4,5,6,7,8-hexahydro-2H-chromene-3-carbonitriles are synthesized by oxidative difunctionalization (geminal dialkoxylation and migration of the amino group) of 2-amino-4-aryl-7,7-dimethyyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitriles in the presence of iodobenzenediacetate in water medium with excellent yields. All the newly synthesized compounds are characterized by IR, ¹H and ¹³C NMR and Mass spectral data. The representative synthesized analogues are screened in vitro for antibacterial and antifungal activity using Gentamycin sulphate and Nystatin as standard drugs.

     

Determination of Phenolic Compounds in Various Propolis Samples Collected from an African and an Asian Region and Their Impact on Antioxidant and Antibacterial Activities

The biological activities of propolis samples are the result of many bioactive compounds present in the propolis. The aim of the present study was to determine the various chemical compounds of some selected propolis samples collected from Palestine and Morocco by the High-Performance Liquid Chromatography–Photodiode Array Detection (HPLC-PDA) method, as well as the antioxidant and antibacterial activities of this bee product. The chemical analysis of propolis samples by HPLC-PDA shows the cinnamic acid content in the Palestinian sample is higher compared to that in Moroccan propolis. The results of antioxidant activity demonstrated an important free radical scavenging activity (2,2-Diphenyl-1-picrylhydrazyl (DPPH); 2,2′-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and reducing power assays) with EC₅₀ values ranging between 0.02 ± 0.001 and 0.14 ± 0.01 mg/mL. Additionally, all tested propolis samples possessed a moderate antibacterial activity against bacterial strains. Notably, Minimum Inhibitory Concentrations (MICs) values ranged from 0.31 to 2.50 mg/mL for Gram-negative bacterial strains and from 0.09 to 0.125 mg/mL for Gram-positive bacterial strains. The S2 sample from Morocco and the S4 sample from Palestine had the highest content of polyphenol level. Thus, the strong antioxidant and antibacterial properties were apparently due to the high total phenolic and flavone/flavonol contents in the samples. As a conclusion, the activities of propolis samples collected from both countries are similar, while the cinnamic acid in the Palestinian samples was more than that of the Moroccan samples.     

Geometric dynamic recrystallization of austenitic stainless steel through linear plane-strain machining

ABSTRACT

Type 316L austenitic stainless steel was severely plastically deformed at room temperature using linear plane-strain machining in a single pass that imparted shear strains up to 2.2 at strain rates up to 2?×?10³ s^?1. The resulting microstructures exhibited significant grain size refinement and improved mechanical strength where geometric dynamic recrystallization was identified as the primary microstructural recrystallization mechanism active at high strain rates. This mechanism is rarely observed in low to medium stacking fault energy materials. The critical stress required for twin initiation is raised by the combined effects of refined grain size and the increase in stacking fault energy due to the adiabatic heating of the chip, thus permitting geometric dynamic recrystallization. The suppression of martensite formation was observed and is correlated to the significant adiabatic heating and mechanical stabilisation of the austenitic stainless steel. A gradient of the amount of strain induced martensite formed from the surface towards the interior of the chip. As the strain rate is increased from 4?×?10² s^?1–2?×?10³ s^?1, a grain morphology change was observed from a population of grains with a high fraction of irregular shaped grains to one dominated by elongated grain shapes with a microstructure characterised by an enhanced density of intragranular sub-cell structure, serrated grain boundaries, and no observable twins. As strain rates were increased, the combination of reduction in strain induced martensite and non-uniform intragranular strain led to grain softening where a Hall-Petch relationship was observed with a negative strengthening coefficient of ?0.08?MPa m^1/2.     

Radial basis function (RBF)‐based parametric models for closed and open curves within the method of regularized stokeslets

The method of regularized Stokeslets (MRS) is a numerical approach using regularized fundamental solutions to compute the flow due to an object in a viscous fluid where inertial effects can be neglected. The elastic object is represented as a Lagrangian structure, exerting point forces on the fluid. The forces on the structure are often determined by a bending or tension model, previously calculated using finite difference approximations. In this paper, we study spherical basis function (SBF), radial basis function (RBF), and Lagrange–Chebyshev parametric models to represent and calculate forces on elastic structures that can be represented by an open curve, motivated by the study of cilia and flagella. The evaluation error for static open curves for the different interpolants, as well as errors for calculating normals and second derivatives using different types of clustered parametric nodes, is given for the case of an open planar curve. We determine that SBF and RBF interpolants built on clustered nodes are competitive with Lagrange–Chebyshev interpolants for modeling twice‐differentiable open planar curves. We propose using SBF and RBF parametric models within the MRS for evaluating and updating the elastic structure. Results for open and closed elastic structures immersed in a 2D fluid are presented, showing the efficacy of the RBF–Stokeslets method. Copyright © 2015 John Wiley & Sons, Ltd.     

Ferroelectric Liquid Crystals: Synthesis and Thermal Behavior of Optically Active,Three‐Ring Schiff Bases and Salicylaldimines

The chiral ferroelectric smectic C (SmC*) phase, characterized by a helical superstructure, has been well exploited in developing high‐resolution microdisplays that have been effectively employed in the fabrication of a wide varieties of portable devices. Although, an overwhelming number of optically active (chiral) liquid crystals (LCs) exhibiting a SmC* phase have been designed and synthesized, the search for new systems continues so as to realize mesogens capable of meeting technical necessities and specifications for their end‐use. In continuation of our research work in this direction, herein we report the design, synthesis, and thermal behavior of twenty new optically active, three‐ring calamitic LCs belonging to four series. The first two series comprise five pairs of enantiomeric Schiff bases whereas the other two series are composed of five pairs of enantiomeric salicylaldimines. In each pair of optical isomers, the configuration of a chiral center in one stereoisomer is opposite to that of the analogous center in the other isomer as they are derived from (3 S)‐3,7‐dimethyloctyloxy and (3 R)‐3,7‐dimethyloctyloxy tails. To probe the structure–property correlations in each series, the length of the n‐alkoxy tail situated at the other end of the mesogens has been varied from n‐octyloxy to n‐dodecyloxy. The measurement of optical activity of these chiral mesogens was carried out by recording their specific rotations. As expected, enantiomers rotate plane polarized light in the opposite direction but by the same magnitude. The thermal behavior of the compounds was established by using a combination of optical polarizing microscopy, differential scanning calorimetry, and powder X‐ray diffraction. These complementary techniques demonstrate the existence of the expected, thermodynamically stable, chiral smectic C (SmC*) LC phase besides blue phase I/II (BPI or BPII) and chiral nematic (N*) phase. However, as noted in our previous analogous study, the vast majority of the Schiff bases show an additional metastable, unfamiliar smectic (SmX) phase just below the SmC* phase. Notably, the SmC* phase persists over the temperature range ≈80–115 °C. Two mesogens chosen each from Schiff bases and salicylaldimines were investigated for their electrical switching behavior. The study reveals the ferroelectric switching characteristics of the SmC* phase featuring the spontaneous polarization (P_S) in the range 69–96 nC cm^?2. The helical twist sense of the SmC* phase as well as the N* phase formed by a pair of enantiomeric Schiff bases and salicylaldimines has been established with the help of circular dichroism (CD) spectroscopic technique. As expected, the SmC* and the N* phase of a pair of enantiomers showed mirror image CD signals. Most importantly, the reversal of helical handedness from left to right and vice versa has been evidenced during the N* to SmC* phase transition, implying that the screw sense of the helical array of the N* phase and the SmC* phase of an enantiomer is opposite.     

The crystal structure of a novel product from the acid-catalyzed condensation of 1-benzylindole with acetone

The acid-catalyzed condensation of 1-benzylindole with acetone in the presence of N-phenylmaleimide gave a tetrahydrocarbazole, (4,5,10,10b-tetrahydro-5-methyl-2-phenyl-10-(phenylmethyl)pyrrolo[3,4-a]carbazole-1,3[2H, 3aH]-dione (1), as the major product and a novel spiro compound, 1,3,4,4-tetrahydro-1,1,3,3-tetramethyl-4,4-bis(phenylmethyl)-1,3(2H, 2H)-spiro[cyclopent[b]indole] (2), as the minor product. The structure of the spiro compound was determined by an X-ray crystallographic determination. The acid-catalyzed condensation of 1-benzylindole with acetone in the absence of N-phenylmaleimide gave a bisindole, (1,1-bis(phenylmethyl)-3,3-(1-methylethylidene)diindole (3), as the major product and the spiro-compound as the minor product.     

Green protocol for conjugate addition of amines to p-quinones accelerated by water

Amines undergo smooth conjugate addition to p-quinones in H₂O at ambient temperature in the absence of a catalyst to produce 2-aminoquinones in excellent yields. Significant rate acceleration of this reaction is observed in H₂O compared to organic solvents. H₂O played a dual role in simultaneously activating the p-quinone and amine. This new methodology constitutes an easy, highly efficient, and green synthesis of substituted p-quinones. Correspondence: J. S. Yadav, Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India.     

Synthesis of 1,2,4-oxadiazole-linked orthogonally urethane-protected dipeptide mimetics

The synthesis of a new class of 1,2,4-oxadiazole-linked orthogonally urethane-protected dipeptide mimetics is described. The protocol employs a reaction between an N-protected amino acyl fluoride and an amino acid-derived amidoxime. All the three commonly employed urethanes have been used in this protocol for N-protection. The course of the reaction was found to be high yielding and all new compounds were well characterized by NMR and mass spectroscopy. The O-acyl amidoxime intermediate has also been isolated as a stable solid.