雪花胺类化合物的三维构效关系研究

雪花胺是一类重要的乙酰胆碱脂酶抑制剂，有可能发展成治疗阿尔茨海默病的药物. 利用分子力学计算得到了这类化合物的优势构象，并对这些化合物进行了CoMFA研究．发现，对于雪花胺类化合物，影响其药效的主要因素是空间结构，电荷作用力的影响较小．对空间因素的进一步分析发现，对于该类分子，不宜用空阻较大的基团进行取代．由电荷影响的分析得到了在不同位置上取代基所应有的电荷性质．三维定量构效关系研究为基于雪花胺的抑制剂设计提供了方案．     

Chiral resolution,absolute configuration determination,and stereo-activity relationship study of IDO1 inhibitor NLG919

NLG919 (1) with two chiral carbon atoms on its chemical structure is a potent indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor. We developed an effective way to prepare all stereoisomers of 1, the key step being the chiral resolution of racemic intermediate 2. The optimal resolution solvent system was identified as dichloromethane and n-pentane or petroleum ether. Using (?)-di-p-toluoyl-d-tartaric acid as resolution reagent, optical pure (R)-2 (e.e.?>?99%, yield?=?70%) was obtained. The mechanism of chiral resolution was clarified through single-crystal X-ray diffraction of the diastereomeric salt. The absolute configurations of four stereoisomers of 1 were established through electronic circular dichroism spectra, quantum chemical calculation and transition metal method. Their IDO1 inhibitory activity was assessed by pharmacological experiments in vitro and in mouse, demonstrating that S configuration of C5 played an important role on the inhibition of IDO1, while the stereochemistry on C2′ exerted little effect on the IDO1 inhibitory activity in mouse.     

CALB-Catalyzed Two-Step Alcoholytic Desymmetrization of 3-Methylglutaric Diazolides in MTBE

Optically pure 3-substituted glutarates can be prepared from the alcoholic ring-opening of cyclic anhydride derivatives, esterification of 3-substituted glutaric acid, and hydrolysis, alcoholysis, aminolysis, and ammonolysis of the diester derivatives via hydrolases or organocatalysts. Unfortunately, most of them mainly focus on the first-step desymmetrization, leading to the difficulty on producing optically pure enantiomers. As a general trend in lipase-catalyzed desymmetrization of 3-methylglutarates, poorer enantiomeric excesses with lower chemical yields were found, as the methyl substituent is relatively small to induce a high enzyme stereodiscrimination. The two-step desymmetrization for CALB-catalyzed alcoholysis of 3-methylglutaric di-1,2,4-triazolide 1a in anhydrous MTBE is first developed to increase the enzyme activity in each reaction step. The enantioselectivity for the second-step kinetic resolution is furthermore improved by using 3-methylglutaric dipyrazolide 1b as the substrate. The kinetic and thermodynamic analysis is, moreover, addressed for shedding insights into the desymmetrization process.     

Paper-based all-solid-state flexible asymmetric micro-supercapacitors fabricated by a simple pencil drawing methodology

A simple and novel methodology was developed for manufacturing interdigitated asymmetric all-solid-state flexible micro-supercapacitors (MSCs) by a facile pencil drawing process followed by electrodepositing MnO₂ on one of the as-drawn graphite electrode as anode and the other as cathode.     

Investigation on enthalpies of combustion and heat capacities for 2-aminomethylpyridine derivatives

Journal of Thermal Analysis and Calorimetry - The molar energies of combustion $$\left( {\Delta_{\text{c}} U_{\text{m}} } \right)$$ for 2-aminomethylpyridine (AMP), tert-butyl...     

Direct C−H Arylation Meets Perovskite Solar Cells: Tin‐Free Synthesis Shortcut to High‐Performance Hole‐Transporting Materials

In contrast to the traditional multistep synthesis, we demonstrate herein a two‐step synthesis shortcut to triphenylamine‐based hole‐transporting materials (HTMs) through sequential direct C?H arylations. These hole‐transporting molecules are fabricated in perovskite‐based solar cells (PSCs) that exhibit promising efficiencies up to 17.69 %, which is comparable to PSCs utilizing commercially available 2,2′,7,7′‐tetrakis[N,N‐di(4‐methoxyphenyl)amino]‐9,9′‐spirobifluorene (spiro‐OMeTAD) as the HTM. This is the first report describing the use of step‐saving C?H activations/arylations in the facile synthesis of small‐molecule HTMs for perovskite solar cells.     

Risk factor extraction with quantile regression method

Firm characteristics based risk factors constitute a large part of the asset pricing literature. These characteristic based factors are constructed using the extreme quantiles of the sorted portfolios based on the firm characteristic in question. Yet to date, there is no consensus on a systematic approach to determine the optimal quantile used for extracting firm characteristic based risk factors. In addition, it is a stylised fact that asset prices exhibit heteroscedastic behavior, and counting on the extreme portfolios to extract the characteristic factors can produce unexpected result. In this study, we use quantile regressions to determine the optimal quantiles used in portfolios sorts to extract characteristic based risk factors used in asset pricing. Quantile regressions are well-suited to identify the quantiles needed to extract firm characteristic based factors, especially when the firm characteristic based factors and stock returns relationship is non-linear. More over, quantile regressions presents the quantile-by-quantile risk-return coefficients, thereby verifying the behavior of the extreme quantiles used in the factor construction. By examining the relationship between common characteristic based factors and stock returns in 23 developed countries, we observed that the optimal quantiles used to construct the common factors may differ between factors, but is similar across the North American, Asia-Pacific and Europe regions.

     

SAND: an AND-RX Feistel lightweight block cipher supporting S-box-based security evaluations

Designs, Codes and Cryptography - We revisit designing AND-RX block ciphers, that is, the designs assembled with the most fundamental binary operations—AND, Rotation and XOR operations and do...     

Nmp-based ionic liquids: Recyclable catalysts for both hetero-Michael addition and Knoevenagel condensation in water

A series of novel N-methyl piperidine (Nmp)-based ionic liquids with 1,2-propanediol group are synthesized and used as catalysts for both hetero-Michael addition of α,β-unsaturated amides and Knoevenagel condensation at room temperature in water; and all the examined substrates could be transformed into corresponding products in good to excellent yields. Meanwhile IL-catalyzed hetero-Michael addition of α,β-unsaturated amides in water has not been reported in the previous literatures. Additionally, the catalyst is recyclable for the two reactions. This finding provides a green catalyst for both hetero-Michael addition of α,β-unsaturated amides and Knoevenagel condensation in water.