From terminal alkynes directly to branched amines

The one-pot synthesis of several branched secondary aliphatic amines is described. Hydroamination of terminal alkynes with aliphatic primary amines in the presence of Cp₂Ti(η²-Me₃SiCCSiMe₃) gives the corresponding aldimines as intermediates. Reaction of these in situ produced aldimines with organolithium reagents (n-BuLi, PhLi) provides the α-branched amines in an easy way in upto 78% overall yield.     

Biologically active compounds through catalysis: efficient synthesis of N-(heteroarylcarbonyl)-N'-(arylalkyl)piperazines

A practical route for the synthesis of new biologically active 5-HT(2 A) receptor antagonists has been developed. In only three catalytic steps, this class of central nervous system (CNS) active compounds can be synthesized efficiently with high diversity. As the initial step, an anti-Markovnikov addition of amines to styrenes provides an easy route to N-(arylalkyl)piperazines, which constitute the core structure of the active molecules. Here, base-catalyzed hydroamination reactions of styrenes with benzylated piperazine proceeded in high yield even at room temperature. After catalytic debenzylation, the free amines were successfully carbonylated with different aromatic and heteroaromatic halides and carbon monoxide to yield the desired compounds in good to excellent yields. The two key reactions, base-catalyzed hydroamination of styrenes and palladium-catalyzed aminocarbonylation of haloarenes/heterocycles, showed tolerance towards various functional groups, thereby demonstrating the potential to synthesize a wide variety of new derivatives of this promising class of pharmaceuticals.     

Penultimate Approximations in Statistics of Extremes and Reliability of Large Coherent Systems

In reliability theory any coherent system can be represented as either a series-parallel or a parallel-series system. Its lifetime can thus be written as the minimum of maxima or the maximum of minima. For large-scale coherent systems it is sensible to assume that the number of system components goes to infinity. Then, the possible non-degenerate extreme value laws either for maxima or for minima are eligible candidates for the system reliability or at least for the finding of adequate lower and upper bounds for the reliability. The identification of the possible limit laws for the system reliability of homogeneous series-parallel (or parallel-series) systems has already been done under different frameworks. However, it is well-known that in most situations such non-degenerate limit laws are better approximated by an adequate penultimate distribution. Dealing with regular and homogeneous parallel-series systems, we assess both theoretically and through Monte-Carlo simulations the gain in accuracy when a penultimate approximation is used instead of the ultimate one.     

The Effects of Food on Cannabidiol Bioaccessibility

Cannabidiol (CBD) is a hydrophobic non-psychoactive compound with therapeutic characteristics. Animal and human studies have shown its poor oral bioavailability in vivo, and the impact of consuming lipid-soluble CBD with and without food on gut bioaccessibility has not been explored. The purpose of this research was to study the bioaccessibility of CBD after a three-phase upper digestion experiment with and without food, and to test lipase activity with different substrate concentrations. Our results showed that lipase enzyme activity and fatty acid absorption increased in the presence of bile salts, which may also contribute to an increase in CBD bioaccessibility. The food matrix used was a mixture of olive oil and baby food. Overall, the fed-state digestion revealed significantly higher micellarization efficiency for CBD (14.15 ± 0.6% for 10 mg and 22.67 ± 2.1% for 100 mg CBD ingested) than the fasted state digestion of CBD (0.65 ± 0.7% for 10 mg and 0.14 ± 0.1% for 100 mg CBD ingested). The increase in bioaccessibility of CBD with food could be explained by the fact that micelle formation from hydrolyzed lipids aid in bioaccessibility of hydrophobic molecules. In conclusion, the bioaccessibility of CBD depends on the food matrix and the presence of lipase and bile salts.     

Domestication of Plants of Ugni molinae Turcz (Myrtaceae) Interferes in the Biology of Chilesia rudis (Lepidoptera: Erebidae) Larvae

In terms of the domestication process in murtilla, studies have found changes in the concentration of phenolic compounds, with reduction of chemical defense of plants, depending on the change in the feeding behavior of insects. Thus, we hypothesized that the domestication of Ugni molinae decreases the content of phenolic compounds and modifies the feeding preference of Chilesia rudis larvae. Leaves of three parental ecotypes and four cultivated ecotypes were used in preference experiments to evaluate the mass gain and leaves consumption of larvae. Phenolic extracts from leaves of U. molinae were analyzed by HPLC. Identified compounds were incorporated in an artificial diet to assess their effect on mass gain, consumption, and survival of the larvae. The presence of phenolic compounds in bodies and feces was also evaluated. In terms of choice assays, larvae preferred parental ecotypes. Regarding compounds, vanillin was the most varied between the ecotypes in leaves. However, plant domestication did not show a reduction in phenolic compound concentration of the ecotypes studied. Furthermore, there was no clear relation between phenolic compounds and the performance of C. rudis larvae. Whether this was because of sequestration of some compounds by larvae is unknown. Finally, results of this study could also suggest that studied phenolic compounds have no role in the C. rudis larvae resistance in this stage of murtilla domestication process.     

Synthesis,structural analysis,and photophysical properties of bi-1,2,3-triazoles

Structural Chemistry - Structural insights of a group of bi-1,2,3-triazoles derived from oxidative CuAAC are described through an X-ray crystallography study, distinguishing a dihedral angle which...     

The Bootstrap Methodology in Statistics of Extremes—Choice of the Optimal Sample Fraction

The main objective of statistics of extremes is the prediction of rare events, and its primary problem has been the estimation of the tail index , usually performed on the basis of the largest k order statistics in the sample or on the excesses over a high level u. The question that has been often addressed in practical applications of extreme value theory is the choice of either k or u, and an adaptive estimation of . We shall be here mainly interested in the use of the bootstrap methodology to estimate adaptively, and although the methods provided may be applied, with adequate modifications, to the general domain of attraction of G, , we shall here illustrate the methods for heavy right tails, i.e. for > 0. Special relevance will be given to the use of an auxiliary statistic that is merely the difference of two estimators with the same functional form as the estimator under study, computed at two different levels. We shall also compare, through Monte Carlo simulation, these bootstrap methodologies with other data-driven choices of the optimal sample fraction available in the literature.     

Using Berry's phase to detect the Unruh effect at lower accelerations

We show that a detector acquires a Berry phase due to its motion in spacetime. The phase is different in the inertial and accelerated case as a direct consequence of the Unruh effect. We exploit this fact to design a novel method to measure the Unruh effect. Surprisingly, the effect is detectable for accelerations 10(9) times smaller than previous proposals sustained only for times of nanoseconds.     

Semi-Parametric Probability-Weighted Moments Estimation Revisited

In this paper, for heavy-tailed models and through the use of probability weighted moments based on the largest observations, we deal essentially with the semi-parametric estimation of the Value-at-Risk at a level p, the size of the loss occurred with a small probability p, as well as the dual problem of estimation of the probability of exceedance of a high level x. These estimation procedures depend crucially on the estimation of the extreme value index, the primary parameter in Statistics of Extremes, also done on the basis of the same weighted moments. Under regular variation conditions on the right-tail of the underlying distribution function F, we prove the consistency and asymptotic normality of the estimators under consideration in this paper, through the usual link of their asymptotic behaviour to the one of the extreme value index estimator they are based on. The performance of these estimators, for finite samples, is illustrated through Monte-Carlo simulations. An adaptive choice of thresholds is put forward. Applications to a real data set in the field of insurance as well as to simulated data are also provided.     

Penultimate limiting forms in extreme value theory

Summary Let {X _n}_n≧1 be a sequence of independent, identically distributed random variables. If the distribution function (d.f.) ofM _n=max (X ₁,…,X _n), suitably normalized with attraction coefficients {α_n}_n≧1(α_n>0) and {b _n}_n≧1, converges to a non-degenerate d.f.G(x), asn→∞, it is of interest to study the rate of convergence to that limit law and if the convergence is slow, to find other d.f.'s which better approximate the d.f. of(M _n−b_n)/a_n thanG(x), for moderaten. We thus consider differences of the formF ⁿ(a_nx+b_n)−G(x), whereG(x) is a type I d.f. of largest values, i.e.,G(x)≡Λ(x)=exp (-exp(−x)), and show that for a broad class of d.f.'sF in the domain of attraction of Λ, there is a penultimate form of approximation which is a type II [Ф _α(x)=exp (−x^−α), x>0] or a type III [Ψ _α(x)= exp (−(−x)^α), x<0] d.f. of largest values, much closer toF ⁿ(a_nx+b_n) than the ultimate itself.