Synthesis of a hexahydropyrimido[1,2-a]azepine-2-carboxamide derivative useful as an HIV integrase inhibitor

The hexahydropyrimido[1,2-a]azepine-2-carboxamide derivative 1 could be obtained by three synthetic strategies, which allowed access to multigram amounts of material of high purity and ee. Two strategies involved alternative approaches to the bicyclic pyrimidone core, with the most efficient one being a two-step sequence from commercially available starting materials exploiting a little precedented cyclisation reaction. The remaining steps to 1 included an efficient crystallisation of an intermediate as a single stereoisomer. An alternative strategy employing a chiral starting material led to products of low optical purity but allowed the assignment of the configuration of the stereogenic centre of 1.     

ESR, electrochemical, molecular modeling and biological evaluation of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones as potential anti-Trypanosoma cruzi agents

Electrochemical and ESR studies were carried out in this work with the aim of characterizing the reduction mechanisms of 4-substituted and 1,4-disubstituted 7-nitroquinoxalin-2-ones by means of cyclic voltammetry in DMSO as aprotic solvent. Two reduction mechanisms were found for these compounds: the first, for compounds bearing a labile hydrogen by following a self-protonation mechanism (ECE steps), and the second, for compounds without labile hydrogen, based on a purely electrochemical reduction mechanism (typical of nitroheterocycles). The electrochemical results were corroborated using ESR spectroscopy allowing us to propose the hyperfine splitting pattern of the nitro-radical, which was later corroborated by the ESR simulation spectra. All these compounds were assayed as growth inhibitors against Trypanosoma cruzi: first, on the non-proliferative (and infective) form of the parasite (trypomastigote stage), and then, the ones that displayed activity, were assayed on the non-infective form (epimastigote stage). Thus, we found four new compounds highly active against T. cruzi. Finally, molecular modeling studies suggest the inhibition of the trypanothione reductase like one of the possible mechanisms involved in the trypanocidal action.     

Multienzymatic Sucrose Conversion into Fructose and Gluconic Acid through Fed-Batch and Membrane-Continuous Processes

Multienzymatic conversion of sucrose into fructose and gluconic acid was studied through fed-batch and continuous (in a membrane reactor) processes. The law of substrate addition (sucrose or glucose) for the fed-batch process which led to a yield superior to 80% was the decreasing linear type, whose feeding rate (?; L/h) was calculated through the equation: ? = ?_o ? k.t, where ?_o (initial feeding rate, L/h), k (linear addition constant, L/h ²), and t (reaction time, h). In the continuous process, the yield of conversion of sucrose (Y) was superior to 70% under the following conditions: dilution rate?=?0.33 h^?1, total duration of 15 h, pH 5.0, 37 °C and initial sucrose concentration of 64 g/L (Y?=?92%), 100 g/L (Y?=?83%), or 150 g/L (Y?=?76%).     

Metamorphosis of a Commodity Plastic like PVC to Efficient Catalytic Single-Chain Nanoparticles

We perform the conversion of a commodity plastic of common use in pipes, window frames, medical devices, flexible hoses, etc. like polyvinyl chloride (PVC) to single-chain nanoparticles (SCNPs). SCNPs are versatile, protein-mimetic soft nano-objects of growing interest for catalysis, sensing, and nanomedicine, among other uses. We demonstrate that the metamorphosis process -as induced through metal-free click chemistry- leads to well-defined, uniform SCNPs that are stable during storage in the solid state for months. All the conversion process (from PVC isolation to PVC-SCNPs synthesis) can be run in a green, dipolar aprotic solvent and involving, when required, a simple mixture of ethanol and water (1/1 vol.) as non-solvent. The resulting PVC-SCNPs are investigated as recyclable, metalloenzyme-mimetic catalysts for several representative Cu(II)-catalyzed organic reactions. The method could be valid for the metamorphosis and valorization of other commodity plastics in which it is feasible to install azide functional groups in their linear polymer chains.     

Stereospecific Photoredox-Catalyzed Vinylations to Functionalized Alkenes and C-Glycosides**

We report an efficient radical-mediated C−C coupling through photoredox-catalyzed reactions of 4-alkyl-dihydropyridines (DHPs) and vinylbenziodoxol(on)es (VBX, VBO). This transition-metal-free and mild photocatalytic method has excellent functional group tolerance and affords vinylated products in good yields, with complete retention of the alkene configuration. The utility of the methodology is demonstrated by the diastereoselective synthesis of C-vinyl glycosides. Preliminary mechanistic studies suggest that the C−C bond formation is stereospecific and proceeds through a concerted radical coupling transition state.     

A study about the solution of convection–diffusion–reaction equation with Danckwerts boundary conditions by analytical,method of lines and Crank–Nicholson techniques

We compare different solutions of the convection–diffusion–reaction problem with Danckwerts boundary conditions. Analytical solution is found, and method of lines and Crank–Nicholson method are described, applied, and compared for different values of Péclet and Damköhler numbers. The eigenvalues and eigenfunctions have been obtained for all the possible values of the dimensionless parameters. And the analytical expression of the concentration has been calculated with the optimum number of terms in the Fourier expansion.     

Asymptotic approximation of a highly oscillatory integral with application to the canonical catastrophe integrals

We consider the highly oscillatory integral $F(w):={\int }_{-\infty }^{\infty }{e}^{iw(t^{K+2}+e^{i\theta }{t}^p)}g(t)dt$ for large positive values of w, , K and p positive integers with $1\le p\le K$, and $g(t)$ an entire function. The standard saddle point method is complicated and we use here a simplified version of this method introduced by López et al. We derive an asymptotic approximation of this integral when $w\to +\infty$ for general values of K and p in terms of elementary functions, and determine the Stokes lines. For $p\ne 1$, the asymptotic behavior of this integral may be classified in four different regions according to the even/odd character of the couple of parameters K and p; the special case $p=1$ requires a separate analysis. As an important application, we consider the family of canonical catastrophe integrals ${\mathrm{\Psi }}_K(x_1,x_2,\text{…},x_K)$ for large values of one of its variables, say $x_p$, and bounded values of the remaining ones. This family of integrals may be written in the form $F(w)$ for appropriate values of the parameters w, θ and the function $g(t)$. Then, we derive an asymptotic approximation of the family of canonical catastrophe integrals for large $|x_p|$. The approximations are accompanied by several numerical experiments. The asymptotic formulas presented here fill up a gap in the NIST Handbook of Mathematical Functions by Olver et al.