The cyclodimerisation of 3-methyl-2-butenenitrile

3-Methyl-2-butenenitrile (1) cyclodimerised on treatment with lithium diisopropylamide in dimethoxyethane at temperatures between ?78°C and 0°C to 3-amino-4-cyano-1,5,5-trimethyl-1,3-cyclohexadiene (2) the structure of which was established by acid hydrolysis to the known 4-cyano-1,5,5-trimethyl-1-cyclohexene-3-one (3).     

Structure-Based Design,Synthesis, and Biological Evaluation of Hsp90β-Selective Inhibitors

The 90 kDa heat shock proteins (Hsp90) are molecular chaperones that are responsible for the folding and/or trafficking of ∼400 client proteins, many of which are directly associated with cancer progression. Consequently, inhibition of Hsp90 can exhibit similar activity as combination therapy as multiple signaling nodes can be targeted simultaneously. In fact, seventeen small-molecule inhibitors that bind the Hsp90 N-terminus entered clinical trials for the treatment of cancer, all of which exhibited pan-inhibitory activity against all four Hsp90 isoforms. Unfortunately, most demonstrated undesired effects alongside induction of the pro-survival heat shock response. As a result, isoform-selective inhibitors have been sought to overcome these detriments. Described herein is a structure-based approach to design Hsp90β-selective inhibitors along with preliminary SAR. In the end, compound 5 was shown to manifest ∼370-fold selectivity for Hsp90β versus Hsp90α, and induced the degradation of select Hsp90β-dependent clients. These data support the development of Hsp90β-selective inhibitors as a new paradigm to overcome the detriments associated with pan-inhibition of Hsp90.     

Design,synthesis, and biological activity studies of a new class of sulfonated aurones: First synthesis of acidoaurone isolated from Phyllanthus acidus

A novel series of aurones were designed by introducing sulfonic acid group on ring-A and ring-B of known natural aurones such as hispidol, sulfuretin, maritimetin, and aureusidin. These sulfonated aurones were synthesized by a unique approach. Sulfonation on ring-A or ring-B converts water-insoluble aurones into highly water-soluble aurones. The sulfonated aurones were tested for their antioxidant, antiinflammatory, and AChE inhibition activities along with their natural aurones. Ring-A sulfonated aurones displayed higher antioxidant activity, 5-LOX, and AChE inhibition in comparison with their corresponding natural aurones. Ring-B sulfonated aurones exhibited potent 5-LOX inhibitory activity and significant antioxidant activity. Acidoaurone, a first sulfonated aurone isolated from Phyllanthus acidus was synthesized for the first time and was well characterized using NMR, LC–MS, and further confirmed by HMBC.     

Shock Processing of Amino Acids Leading to Complex Structures—Implications to the Origin of Life

The building blocks of life, amino acids, are believed to have been synthesized in the extreme conditions that prevail in space, starting from simple molecules containing hydrogen, carbon, oxygen and nitrogen. However, the fate and role of amino acids when they are subjected to similar processes largely remain unexplored. Here we report, for the first time, that shock processed amino acids tend to form complex agglomerate structures. Such structures are formed on timescales of about 2 ms due to impact induced shock heating and subsequent cooling. This discovery suggests that the building blocks of life could have self-assembled not just on Earth but on other planetary bodies as a result of impact events. Our study also provides further experimental evidence for the ‘threads’ observed in meteorites being due to assemblages of (bio)molecules arising from impact-induced shocks.     

Conical parametric scattering of a single extraordinary beam in BaTiO3 crystal

In this paper, the parametric scattering of a single extraordinary polarized beam of laser in BaTiO₃ photorefractive crystal has been investigated experimentally and theoretically. The resulting pattern consists of beam fanning, isotropic ring, and anisotropic one. Among all parts of scattering pattern, isotropic ring has not been studied as much as beam fanning and anisotropic ring, and there still are some differences in reports about it. Therefore, the study has mainly focused on this part. In this experimental configuration, isotropic ring is just visible in positive angles although the other parts of parametric scattering pattern can be visible from behind and in front of the crystal. In addition to steady state pattern in forward and backward directions, its transient behavior with the rotation of crystal has been studied. The results of experiments have been analyzed carefully, and their theoretical explanations have been presented based on the standard theory of parametric scattering in photorefractive crystals. It has been shown that this configuration corresponds to the so called parametric B-process scattering.     

Unusual nucleation and growth of γ′ iron nitride upon nitriding Fe–4.75 at.% Al alloy

The influence of substitutionally dissolved Al in ferritic Fe–4.75 at.% Al alloy on the nucleation and growth of γ′ iron nitride (Fe₄N_{1? x} ) was investigated upon nitriding in NH₃/H₂ gas mixtures. The nitrided specimens were characterised employing optical microscopy, scanning electron microscopy, transmission electron microscopy, electron probe microanalysis and X-ray diffraction. As compared to the nitriding of pure ferrite (α-Fe), where a layer of γ′ develops at the surface, upon nitriding ferritic Fe–4.75 at.% Al an unusual morphology of γ′ plates develops at the surface, which plates deeply penetrate the substrate. In the diffusion zone, nano-sized precipitates of γ′ and of metastable, cubic (NaCl-type) AlN occur, having, with the ferrite matrix, a Nishiyama–Wassermann orientation relationship and a Bain orientation relationship, respectively. The γ′ plates contain a high density of stacking faults and fine ε iron nitride (Fe₂N_{1? z} ) precipitates, although the formation of ε iron nitride is not expected for the employed nitriding parameters. On the basis of dedicated nitriding experiments it is shown that the unusual microstructural development is a consequence of the negligible solubility of Al in γ′ and the obstructed precipitation of the thermodynamically stable, hexagonal (wurtzite-type) AlN in ferrite.     

Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-one reexamined: formation of isomeric angular fused quinazolinoquinazolinones and their spectroscopic identification

Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-ones on to N₃ and on to N₁ leading to 6-alkyl-(8H)-quinazolino[4,3-b]quinazolin-8-one and 6-alkyl-(13H)-quinazolino[3,4-a]quinazolin-13-one, respectively was described for the first time. The differences in the IR and carbon NMR data of these isomeric fused quinazolinoquinazolinones afford a useful method for distinguishing between the two series.     

Self-chemical ionization of diethylzinc

The self-chemical ionization of diethylzinc is examined by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry and semiempirical molecular orbital calculations. Electron impact of diethylzinc neutral produces the radical cation, C(4)H(15)Zn(+) (m/z x 122), which reacts further with the neutral (C(2)H(5))(2)Zn to give the following product ions: Zn(+) (m/z x 64), C(2)H(5)Zn(+) (m/z x 93), C(4)H(9)Zn(+) (m/z x 121), C(4)H(11)Zn(2)(+) (m/z x 187), and C(6)H(15)Zn(2)(+) (m/z x 215). To determine the structure and pathways for production of these ions, monoisotopic (12)C(4)H(15)(64)Zn(+), (64)Zn(+) and (12)C(2)H(5)(64)Zn(+) were individually isolated and reacted with the neutral background. We also performed semiempirical molecular orbital calculations (ZINDO/1). The molecular orbital calculations and experimental data are consistent in predicting that the ethyl group on the diethylzinc cation carries the positive charge. Copyright 1999 John Wiley & Sons, Ltd.     

Continuous and discontinuous precipitation in Fe-1 at.%Cr-1 at.%Mo alloy upon nitriding; crystal structure and composition of ternary nitrides

The internal nitriding response of a ternary Fe–1 at.%Cr–1 at.%Mo alloy, which serves as a model alloy for many CrMo-based steels, was investigated. The nitrides developing upon nitriding were characterised by X-ray diffraction, scanning electron microscopy, electron probe microanalysis, transmission electron microscopy and atom probe tomography. The developed nitrides were shown to be (metastable) ternary mixed nitrides, which exhibit complex morphological, compositional and structural transformations as a function of nitriding time. Analogous to nitrided binary Fe–Cr and Fe–Mo alloys, in ternary Fe–Cr–Mo alloys initially continuous precipitation of fine, coherent, cubic, NaCl-type nitride platelets, here with the composition (Cr_½,Mo_½)N_¾, occurs, with the broad faces of the platelets parallel to the {1?0?0}_α-Fe lattice planes. These nitrides undergo a discontinuous precipitation reaction upon prolonged nitriding leading to the development of lamellae of a novel, hexagonal CrMoN₂ nitride along {1?1?0}_α-Fe lattice planes, and of spherical cubic, NaCl-type (Cr,Mo)N _x nitride particles within the ferrite lamellae. The observed structural and compositional changes of the ternary nitrides have been attributed to the thermodynamic and kinetic constraints for the internal precipitation of (misfitting) nitrides in the ferrite matrix.     

Competitive cascade cyclization of 2′-tosyloxychalcones: An easy access to thioflavones and thioaurones

Abstract

A new and efficient approach for the synthesis of thioflavones and thioaurones by competitive cascade cyclization of 2′-tosyloxychalcones has been developed. 2′-Tosyloxychalcones were smoothly converted into thioflavones and thioaurones by incorporation of sulfur atom using elemental sulfur and triethylamine in DMSO with good yields. The advantages of the methodology are the formation of both thioflavones and thioaurones in a single step. Easily accessible substrates, mild reaction conditions and compatibility with a broad range of functional groups make this protocol clean and inexpensive.