Review on asymmetric synthetic methodologies for chiral isoquinuclidines; 2008 to date

Isoquinuclidines constitute the central structural nucleus of numerous biologically active natural products, for example, iboga alkaloids such as ibogamine and catharanthine as well as non-indole-containing alkaloids such as the dioscorine and the cannivonines. Furthermore, in medicinal and pharmaceutical chemistry, the isoquinuclidine core is commonly employed as a rigid azabicyclic scaffold, thus providing significant precursors in the synthesis of numerous valuable alkaloids. Summarizing well-organized approaches to access the chiral isoquinuclidine structural centerpiece signifies a significant endeavor not only for developing biologically active natural products but also enhancing biological researches that can lead to possible drug discovery. Over time, the values and methodologies for the asymmetric synthesis of chiral isoquinuclidines are increasing; hence to advance asymmetric synthesis, this review combines and discusses the pros and cons of each synthesis techniques from 2008. This review should be helpful for promoting further developments of asymmetric synthetic methodologies and for medicinal chemistry.     

Mechanochemical synthesis and giant dielectric properties of CaCu3Ti4O12

CaCu₃Ti₄O₁₂ powder has been synthesized by mechanochemical milling (C-m) and solid-state reaction (C-ssr) techniques. C-m powder has a grain size of ~24 nm as determined from X-ray diffraction and FE-SEM measurements. The grain size of C-m ceramics has increased to 20 μm compared to a size of 3 μm for C-ssr ceramics after sintering at 1,050 °C for 10 h. Giant dielectric constant was observed in both ceramics with that of C-m larger than that of C-ssr. Impedance results show that the grain conductivity of C-m is more than two orders of magnitude lower than that of C-ssr, whereas its grain boundary conductivity is larger than that of C-ssr. These results are supported by the EDX results that show Cu-enriched grain boundaries in C-m ceramics.     

Organometallic Derivatization of the Nematocidal Drug Monepantel Leads to Promising Antiparasitic Drug Candidates

The discovery of novel drugs against animal parasites is in high demand due to drug‐resistance problems encountered around the world. Herein, the synthesis and characterization of 27 organic and organometallic derivatives of the recently launched nematocidal drug monepantel (Zolvix^®) are described. The compounds were isolated as racemates and were characterized by ¹H, ¹³C, and ¹⁹F NMR spectroscopy, mass spectrometry, and IR spectroscopy, and their purity was verified by microanalysis. The molecular structures of nine compounds were confirmed by X‐ray crystallography. The anthelmintic activity of the newly designed analogues was evaluated in vitro against the economically important parasites Haemonchus contortus and Trichostrongylus colubriformis. Moderate nematocidal activity was observed for nine of the 27 compounds. Three compounds were confirmed as potentiators of a known monepantel target, the ACR‐23 ion channel. Production of reactive oxygen species may confer secondary activity to the organometallic analogues. Two compounds, namely, an organic precursor ( 3 a ) and a cymantrene analogue ( 9 a ), showed activities against microfilariae of Dirofilaria immitis in the low microgram per milliliter range.     

A rapid approach for the copper,amine, and ligand-free Sonogashira coupling of 4-methyl-7-nonafluorobutylsulfonyloxy coumarins under microwave irradiation

A rapid, efficient, and reliable access for the synthesis of an assortment of 4-methyl-7-alkyl/aryl/heteroaryl alkynyl coumarins has been developed by the copper, amine, and ligand-free Sonogashira cross-coupling reaction of 4-methyl-7-nonafluorobutylsulfonyloxy coumarin with various terminal alkynes under microwave irradiation. In the presence of a suitable catalyst, base, and solvent, the coupling reaction proceeded smoothly to give the diaryl alkynes in satisfactory to exceptional yields. Nonaflates coupled more efficiently than the corresponding triflates which yielded the detriflated product as well as the hydrolyzed product as competing side products along with the required product. The utilization of TBAF·3H₂O as a mild base as well as a solvating agent was the key for success of the reaction.     

Study of three-dimensional deformation of a pallet using phase-shiff shadow moiré and finite-element analysis

We present the results of a comparative study on the static deformation of a pallet, made from oil-palm fiberreinforced composite material, using the phase-shift shadow moiré method and finite-element analysis (FEA). The pallet was designed and analyzed using a commerical software package. The effect of various joint types on the deformation profile was studied to obtain a simplified model to represent the actual design. A one-fifth scale model of the pallet was fabricated and the deformation due to static loading was measured using the phase-shift shadow moiré method. The comparison between the measurement and FEA results on the deformed profile showed a maximum difference of 13.7% at the center of the some of the deck boards, but a smaller difference at other deck boards. The FEA results also produced a larger deformation gradient compared to the measurements.     

Vibration and buckling of laminated sandwich plates having interfacial imperfections

The vibration and buckling characteristics of sandwich plates having laminated stiff layers are studied for different degrees of imperfections at the layer interfaces using a refined plate theory. With this plate theory, the through thickness variation of transverse shear stresses is represented by piece-wise parabolic functions where the continuity of these stresses is satisfied at the layer interfaces by taking jumps in the transverse shear strains at the interfaces. The transverse shear stresses free condition at the plate top and bottom surfaces is also satisfied. The inter-laminar imperfections are represented by in-plane displacement jumps at the layer interfaces and characterized by a linear spring layer model. It is quite interesting to note that this plate model having all these refined features requires unknowns only at the reference plane. To have generality in the analysis, finite element technique is adopted and it is carried out with a new triangular element developed for this purpose, as any existing element cannot model this plate model. As there is no published result on imperfect sandwich plates, the problems of perfect sandwich plates and imperfect ordinary laminates are used for validation.     

Determination of plastic stress-strain behavior by digital-image-processing techniques

This work explores the application of digitalimage-processing techniques to the measurement of large plastic strains. Two sample problems have been selected, namely the uniform tensile deformation of aluminum-sheet metal strips and the post-necking deformation of copper circular rods. Images of these gridded metallic test pleces were captured, digitized and analyzed in a fully computerized way to evaluate strain distributions, anisotropic parameters and plastic stress-strain flow curves. For post-necked test pieces, Bridgman stress correction has been easily applied by defining the neck profile contour from the automated processing of digitized images. Results compare satisfactorily with those based on displacements measured by conventional microscopy. The presented technique, with added improvements, can consititute a viable one for accurate and fully computerized measurement of large deformations.     

Radiation properties of a uniaxial chiral quadratic inhomogeneous slab under oblique incidence

In this paper, the focussing of the transmitted electromagnetic field through a quadric inhomogeneous slab of lossless uniaxial chiral medium is derived using transmission coefficient under oblique incidence. The inhomogeneity in the uniaxial chiral slab has been incorporated through permittivity parameter. Asymptotic ray theory provides valid field everywhere except at focal point where it gives infinite value. Singularity of the field at focal point is addressed using Maslov's method. The derived analytical field expressions at caustic or focal point of uniaxial quadratic inhomogeneous slab have been solved numerically using MATHEMATICA. The effects of chirality parameter, axial permittivity, transvers permittivity, angle of incidence on the refracted field are discussed and the effects of Brewster angle on the focussed field are also discussed. The results obtained using Maslov's method are compared with Huygens–Kirchhoff's integral which are in good agreement.