Chiral amines in the diastereoselective Mannich-related multicomponent synthesis of diarylmethylamines, 1,2-diarylethylamines, and β-arylethylamines

The multicomponent synthesis of diarylmethylamines, 1,2-diarylethylamines and β-arylethylamines has been undergone starting from aryl- or benzylzinc reagents, aldehydes, and primary or secondary chiral amines. Good to high diastereoselectivities have been obtained from both l-proline ester derivatives 1 and (±)-trans-1-allyl-2,5-dimethylpiperazine (4). The use of R-(+)-1-phenylethylamine (7) provides important diastereoisomeric excesses (∼60%) in conjunction with very high chemical yields. This work constitutes a preliminary entry to the intended development of a more flexible reaction system, involving easily cleavable chiral amines.     

Improvement of the traceability of reference materials certified for purity: evaluation of a semi-preparative high-performance liquid chromatography approach

A semi-preparative high-performance liquid chromatography process was evaluated as a tool to quantitatively determine the purity or percentage mass fraction content (% m/m) of organic compounds. The method is simple and does not require the identification and subsequent quantitation of organic-related structure impurities. A protocol was developed and tested on four reference materials certified for purity from 95% m/m to 99.3% m/m. Comparing the purity results of each certified reference material using the new approach with their respective certified values showed no significant analytical bias. Semi-preparative high-performance liquid chromatography has proved the potential to be a primary method directly traceable to mass with an uncertainty statement written down also in terms of mass with expanding uncertainty ranging from 0.8% to 1.3% m/m compared to 0.3 to 2.0% m/m for the certified purity values at the 95% confidence interval.     

Fast and efficient in silico 3D screening: toward maximum computational efficiency of pharmacophore-based and shape-based approaches

In continuation of our recent studies on the quality of conformational models generated with CATALYST and OMEGA we present a large-scale survey focusing on the impact of conformational model quality and several screening parameters on pharmacophore-based and shape-based virtual high throughput screening (vHTS). Therefore, we collected known active compounds of CDK2, p38 MAPK, PPAR-gamma, and factor Xa and built a set of druglike decoys using ilib:diverse. Subsequently, we generated 3D structures using CORINA and also calculated conformational models for all compounds using CAESAR, CATALYST FAST, and OMEGA. A widespread set of 103 structure-based pharmacophore models was developed with LigandScout for virtual screening with CATALYST. The performance of both database search modes (FAST and BEST flexible database search) as well as the fit value calculation procedures (FAST and BEST fit) available in CATALYST were analyzed in terms of their ability to discriminate between active and inactive compounds and in terms of efficiency. Moreover, these results are put in direct comparison to the performance of the shape-based virtual screening platform ROCS. Our results prove that high enrichment rates are not necessarily in conflict with efficient vHTS settings: In most of the experiments, we obtained the highest yield of actives in the hit list when parameter sets for the fastest search algorithm were used.     

Protection of lithium metal surfaces using chlorosilanes

In this paper, we present a new approach for protecting metallic lithium surfaces based on a reaction between the thin native layer of lithium hydroxide present on the surface and various chlorosilane derivatives. The chemical composition of the resulting layer and the chemistry involved in layer formation were analyzed by polarization modulated infrared reflection absorption spectroscopy (PM-IRRAS), X-ray photoelectron spectroscopy (XPS), and energy dispersive X-ray analysis (EDX). Spectroscopy shows the disappearance of surface hydroxide groups and the appearance of silicon and chloride on the lithium surface. Differential scanning calorimetry (DSC) and electrochemical impedance spectroscopy (EIS) show that this surface treatment protects the lithium from certain gas-phase reactions and is ionically conductive.     

High asymmetric induction in diels-alder additions of cyclopentadiene to acrylates derived from isoborneol

Starting from (R)-(+)- and from (S)-(?)-camphor the chiral alcohols $\text{1}$, $\text{2}$ and $\text{3}$ have been prepared; their acrylates II underwent TiCl₂(OR)₂-promoted Diels-Alder additions to cyclopentadiene giving efficiently in a predictable manner either the (2R)- or the (2S)-adducts III with up to virtually quantitative asymmetric induction.     

Sensitivity indices for multivariate outputs

We define and study a generalization of Sobol sensitivity indices for the case of a vector output.     

Evidential reasoning in large partially ordered sets

The Dempster-Shafer theory of belief functions has proved to be a powerful formalism for uncertain reasoning. However, belief functions on a finite frame of discernment Ω are usually defined in the power set 2^Ω, resulting in exponential complexity of the operations involved in this framework, such as combination rules. When Ω is linearly ordered, a usual trick is to work only with intervals, which drastically reduces the complexity of calculations. In this paper, we show that this trick can be extrapolated to frames endowed with an arbitrary lattice structure, not necessarily a linear order. This principle makes it possible to apply the Dempster-Shafer framework to very large frames such as the power set, the set of partitions, or the set of preorders of a finite set. Applications to multi-label classification, ensemble clustering and preference aggregation are demonstrated.     

W01,1 solutions in some borderline cases of Calderon–Zygmund theory

In this paper we study the existence of $W_0^{1,1}(\Omega )$ distributional solutions of Dirichlet problems whose simplest example is$\{\begin{array}{cc}?\mathrm{div}\left({|\mathrm{?}u|}^{p?2}\mathrm{?}u\right)=f(x),\hfill & \text{in}\Omega ;\hfill \\ u=0,\hfill & \text{on}?\Omega .\hfill \end{array}$