Heterocyclization of alicyclic 1,5-diketones. Synthesis of N-substituted 5-(4,5,6,7-tetrahydro-1H-indol-2-yl)pentanoic acids on the basis of (2,2'-methanediyl)biscyclohexanone and primary amines

Chemistry of Heterocyclic Compounds - The bisulfite adduct, formed upon treatment of (2,2'-methanediyl)biscyclohexanone with aqueos sodium bisulfite solution in the presence of acetic acid,...     

Synthesis of ferrocene annulated trifluoromethylated heterocycles with crispine and lamellarin skeletons

Ferrocene analogues of pyrrolo[2,1-a]isoquinoline alkaloids, 2-(trifluoromethyl)-5,6-dihydroferroceno[g]indolizine and 6-(trifluoromethyl)-8,9-dihydro-6H-chromeno[4,3-b]ferroceno[g]indolizines, were obtained in 44–65% yield via the Grob reaction between 1-nitro-1-(2,2,2-trifluoroethylidene)alkanes or 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1-alkyl-3,4-dihydroferroceno[c]pyridines in 2-propanol at reflux.     

Synthesis of 1-(Adamantan-1-yl)-1H-1,2,3-Triazoles and their Salts by Adamantylation in AdOH–HClO4 and AdOH–H2SO4 Systems

Chemistry of Heterocyclic Compounds - 1-(Adamantan-1-yl)-1H-1,2,3-triazoles and a series of 1-(adamantan-1-yl)-3-alkyl-1,2,3-triazolium salts were synthesized by regioselective adamantylation of...     

Acid Catalyzed tert‐Butylation and Tritylation of 4‐Nitro‐1,2,3‐triazole: Selective Synthesis of 1‐Methyl‐5‐nitro‐1,2,3‐triazole via 1‐tert‐Butyl‐4‐nitro‐1,2,3‐triazole

4‐Nitro‐1,2,3‐triazole was found to react with tert‐butanol in concentrated sulfuric acid to yield 1‐tert‐butyl‐4‐nitro‐1,2,3‐triazole as the only reaction product, whereas tert‐butylation and tritylation of 4‐nitro‐1,2,3‐triazole in presence of catalytic amount of sulfuric acid in benzene was found to provide mixtures of isomeric 1‐ and 2‐alkyl‐4‐nitro‐1,2,3‐triazoles with predominance of N2‐alkylated products. A new methodology for preparation of 1‐alkyl‐5‐nitro‐1,2,3‐triazoles from 1‐tert‐butyl‐4‐nitro‐1,2,3‐triazole via exhaustive alkylation followed by removal of tert‐butyl group from intermediate triazolium salts was demonstrated by the example of preparation of 1‐methyl‐5‐nitro‐1,2,3‐triazole.     

Sterol 14alpha-demethylase as a potential target for antitrypanosomal therapy: enzyme inhibition and parasite cell growth

Sterol 14alpha-demethylases (CYP51) serve as primary targets for antifungal drugs, and specific inhibition of CYP51s in protozoan parasites Trypanosoma brucei (TB) and Trypanosoma cruzi (TC) might provide an effective treatment strategy for human trypanosomiases. Primary inhibitor selection is based initially on the cytochrome P450 spectral response to ligand binding. Ligands that demonstrate strongest binding parameters were examined as inhibitors of reconstituted TB and TC CYP51 activity in vitro. Direct correlation between potency of the compounds as CYP51 inhibitors and their antiparasitic effect in TB and TC cells implies essential requirements for endogenous sterol production in both trypanosomes and suggests a lead structure with a defined region most promising for further modifications. The approach developed here can be used for further large-scale search for new CYP51 inhibitors.     

Enhanced thermodynamic and kinetic stability of calix[4]arene dimers locked in the cone conformation

Wide rim tetraurea derivatives (2a,b) have been prepared from a calix[4]arene rigidified in the cone conformation by two diethyleneglycol ether bridges between adjacent oxygens. In comparison to the analogous tetraurea derivatives (3a,b) of a tetrapentoxy calix[4]arene, 2a,b show an increased thermodynamic stability in mixtures of CDCl(3) and DMSO-d(6). Their kinetic stability as expressed by the rate of guest exchange (benzene or cyclohexane against the solvent benzene-d(6)) is also strongly increased by factors of 30-38. Noticeable differences for the inclusion of selected guests are found.     

Triplet Fullerenes as Prospective Spin Labels for Nanoscale Distance Measurements by Pulsed Dipolar EPR Spectroscopy

Precise nanoscale distance measurements by pulsed electron paramagnetic resonance (EPR) spectroscopy play a crucial role in structural studies of biomolecules. The properties of the spin labels used in this approach determine the sensitivity limits, attainable distances, and proximity to biological conditions. Herein, we propose and validate the use of photoexcited fullerenes as spin labels for pulsed dipolar (PD) EPR distance measurements. Hyperpolarization and the narrower spectrum of fullerenes compared to other triplets (e.g., porphyrins) boost the sensitivity, and superior relaxation properties allow PD EPR measurements up to a near‐room temperature. This approach is demonstrated using fullerene–nitroxide and fullerene–triarylmethyl pairs, as well as a supramolecular complex of fullerene with nitroxide‐labeled protein. Photoexcited triplet fullerenes can be considered as new spin labels with outstanding spectroscopic properties for future structural studies of biomolecules.     

A flux-corrected transport algorithm for handling the close-packing limit in dense suspensions

Convection of a scalar quantity by a compressible velocity field may give rise to unbounded solutions or nonphysical overshoots at the continuous and discrete level. In this paper, we are concerned with solving continuity equations that govern the evolution of volume fractions in Eulerian models of disperse two-phase flows. An implicit Galerkin finite element approximation is equipped with a flux limiter for the convective terms. The fully multidimensional limiting strategy is based on a flux-corrected transport (FCT) algorithm. This nonlinear high-resolution scheme satisfies a discrete maximum principle for divergence-free velocities and ensures positivity preservation for arbitrary velocity fields. To enforce an upper bound that corresponds to the maximum-packing limit, an FCT-like overshoot limiter is applied to the converged convective fluxes at the end of each time step. This postprocessing step imposes an additional physical constraint on the numerical solution to the unconstrained mathematical model. Numerical results for 2D implosion problems illustrate the performance of the proposed limiting procedure.     

On the Boundedness of Solutions of Degenerate Anisotropic Elliptic Variational Inequalities

In this article, for a class of degenerate anisotropic elliptic second-order variational inequalities we give conditions on the right-hand side and the set of constraints under which solutions of the variational inequalities are bounded. Our conditions on the set of constraints admit the consideration of a sufficiently large class of problems with pointwise constraints, and in particular, unilateral and bilateral problems. They also admit the consideration of the Dirichlet problem for the corresponding equations. We provide a series of examples which demonstrate the essentiality of the imposed conditions. In particular, we show that the condition assumed for the right-hand side of the variational inequalities in general is unimprovable in the scale of Lebesgue spaces.     

Simple design technique for a triangular FBG filter based on a linearly chirped grating

A novel and simple design technique for triangular spectrum response of fibre Bragg grating (FBG) is presented based on a linear chirped grating. It is shown that this method is fast and can give a straightforward solution to meet a design target. The numerical simulation examples verified the effectiveness of the design method. A general approach to design for multichannel triangular spectral responses for FBG filters is proposed, which provides a solution that achieves a minimum change of refractive index for the fibre.