二氢黄酮类化合物的合成研究进展

综述二氢黄酮类化合物的合成研究进展,总结已报道的各种类型的二氢黄酮合成方法,为二氢黄酮类新药研发提供方法学支持。合成方法包括:查尔酮环合、Friedel-Crafts反应、Knoevenagel缩合和Hoesch单酰基化反应,以及二氢黄酮的不对称合成,并简要介绍无溶剂合成二氢黄酮等"绿色"化学方法。     

Hydrogen‐Bonding Effects for the C–ON Bond Homolysis and Reformation Reactions of Alkoxyamines

N‐(2‐methylpropyl)‐N‐(1‐diethylphosphono‐2,2‐dimethylpropyl)‐O‐(2‐carboxyprop‐2‐yl) hydroxylamine (BlocBuilder MA) is, among the commercially available alkoxyamines, one of the most efficient for nitroxide‐mediated polymerization (NMP). However, recent results have shown that it does not perform well for the NMP of isoprene. The occurrence of intramolecular hydrogen bonding (IHB) between the carboxylic function and the diethoxyphosphoryl group has been proposed as the reason for its low efficiency. In this article, the presence of this IHB is confirmed using IR, ³¹P NMR, ³¹P‐¹H HOESY, and DFT calculation results. The solvent effect on this IHB and consequently on k_d values is also investigated. However, combining kinetic analysis and rate measurements in various solvents, the influence of this IHB on the C? ON bond homolysis and reformation in alkoxyamine is shown to be very weak.

     

Structure and function of cis‐acting RNA elements of flavivirus

The genus Flavivirus is a group of single‐stranded, positive‐sense RNA viruses that includes numerous human pathogens with global impact, such as dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Zika virus (ZIKV). The approximately 11‐kilobase genome is flanked by highly structured untranslated regions (UTRs), which contain various cis‐acting RNA elements with unique structures and functions. Moreover, local RNA elements circularize the genome non‐covalently through long‐range interactions. Interestingly, many flavivirus cis‐acting RNA elements contain group‐specific motifs or are specific for the given phylogenetic groups, suggesting their potential association with flavivirus evolution and diversification. In this review, we summarize recent advances about the structure and function of cis‐acting RNA elements in flavivirus genomes and highlight the potential implications for flavivirus evolution. Finally, the scientific questions remained to be answered in the field are also discussed.     

EPSA: A Novel Supercritical Fluid Chromatography Technique Enabling the Design of Permeable Cyclic Peptides

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4-[(4,4-二甲基-7-甲氧基-1,3-二氧代-异喹啉基)乙基]苯磺酰胺的合成

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Mechanistic studies on the drug metabolism and toxicity originating from cytochromes P450

Abstract

Cytochromes P450 are oxidizing enzymes; a few families of cytochromes P450 are implicated in drug metabolism. These enzymatic reactions involve many processes including (i) prodrug to drug conversion, (ii) easy excretion of drug, (iii) generation of reactive metabolites, many of which cause toxicity. In this review, the fundamental biochemical mechanisms associated with the conversion of drugs into the useful or toxic metabolites have been discussed. The mechanisms can be established with the help of many experimental methods like mass spectral analysis, NMR and in vitro analysis etc. Computational methods provide detailed atomic level information, which is generally not available from experimental studies. Thus, the in silico efforts in elucidating the molecular mechanisms are complementary to the known experimental methods and are often clearer (especially in providing 3D information about the metabolites and their reactions). Quantum chemical methods and molecular docking become especially very useful. This review includes five case studies, which explain how the atomic level details were obtained to explore the reaction mechanisms of drug metabolism by cytochromes P450.     

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