Deconstructive Reorganization: De Novo Synthesis of Hydroxylated Benzofuran

An unprecedented deconstructive reorganization strategy for the de novo synthesis of hydroxylated benzofurans from kojic acid‐ or maltol‐derived alkynes is reported. In this reaction, both the benzene and furan rings were simultaneously constructed, whereas the pyrone moiety of the kojic acid or maltol was deconstructed and then reorganized into the benzene ring as a six‐carbon component. Through this strategy, at least one free hydroxyl group was introduced into the benzene ring in a substitution‐pattern tunable fashion without protection–deprotection and redox adjustment. With this method, a large number of hydroxylated benzofuran derivatives with different substitution‐patterns have been prepared efficiently. This methodology has also been shown as the key step in a collective total synthesis of hydroxylated benzofuran‐containing natural products (11 examples).     

Palladium-Catalyzed Dehalogenation of Benzofuran Bromides

Various benzofuran bromides were dehalogenated using the palladium catalyst and phosphine ligands in the present of 5 equiv water. This set up a new and efficient protocol for the palladium-catalyzed dehalogenation of benzofuran bromides, which could tolerate the presence of water and have selective debromination.     

Transition‐Metal‐Free Deconstructive Lactamization of Piperidines

One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp³)–C(sp³) bonds, which requires using transition or precious metal catalysts. We present here an alternative: the deconstructive lactamization of piperidines without using transition metal catalysts. To this end, we use 3‐alkoxyamino‐2‐piperidones, which were prepared from piperidines through a dual C(sp³)–H oxidation, as transitory intermediates. Experimental and theoretical studies confirm that this unprecedented lactamization occurs in a tandem manner involving an oxidative deamination of 3‐alkoxyamino‐2‐piperidones to 3‐keto‐2‐piperidones, followed by a regioselective Baeyer–Villiger oxidation to give N‐carboxyanhydride intermediates, which finally undergo a spontaneous and concerted decarboxylative intramolecular translactamization.     

Electrochemical Behaviour of Benzofuran Derivatives of Pharmaceutical Interest at Solid Electrodes

Abstract

The electrooxidation of four structually related drugs (amiodarone and benziodarone and their iodinated derivatives), has been studied, using cyclic voltammetry and controlled potential coulometry at carbon paste and platinum electrodes in hydro-organic media. The oxidative mechanisms have been suggested on the basis of a comparative study and by analyzing the i_p, E_p/ pH plots, the number of electrons evolved and the cyclic voltammetric behaviours. The influence of carbon-iodine bonds on the redox pattern of the molecules has been analyzed and a comparison between the oxidation pattern of the phenolic molecules and the corresponding diethylaminoethoxy derivatives has been realized. Quantitative measurements have been obtained at the carbon paste electrode, within the range of concentrations 5. × 10^?6 M - 5 × 10⁵ M. The analytical usefulness in determination of these compounds has been demonstrated.     

Advances in Atroposelectively De Novo Synthesis of Axially Chiral Heterobiaryl Scaffolds

Axially chiral heterobiaryl frameworks are privileged structures in many natural products, pharmaceutically active molecules, and chiral ligands. Therefore, a variety of approaches for constructing these skeletons have been developed. Among them, de novo synthesis, due to its highly convergent and superior atom economy, serves as a promising strategy to access these challenging scaffolds including C-N, C-C, and N-N chiral axes. So far, several elegant reviews on the synthesis of axially chiral heterobiaryl skeletons have been disclosed, however, atroposelective construction of the heterobiaryl subunits by de novo synthesis was rarely covered. Herein, we summarized the recent advances in the catalytic asymmetric synthesis of the axially chiral heterobiaryl scaffold via de novo synthetic strategies. The related mechanism, scope, and applications were also included.     

De Novo Synthesis of Mono‐ and Oligosaccharides via Dihydropyran Intermediates

The importance of carbohydrates is evident by their essential role in all living systems. Their syntheses have attracted attention from chemists for over a century. Most chemical syntheses in this area focus on the preparation of carbohydrates from naturally occurring monosaccharides. De novo chemical synthesis of carbohydrates from feedstock starting materials has emerged as a complementary method for the preparation of diverse mono‐ and oligosaccharides. In this review, the history of de novo carbohydrate synthesis is briefly discussed and particular attention is given to methods that address the formation of glycosidic bonds for potential de novo synthesis of oligosaccharides. Almost all methods of this kind involve the formation of dihydropyran intermediates. Recent progress in forming dihydropyrans by Achmatowicz rearrangement, hetero‐Diels–Alder cycloaddition, ring‐closing metathesis, and other methods is also elaborated.     

De Novo Synthesis of Furanose Sugars: Catalytic Asymmetric Synthesis of Apiose and Apiose‐Containing Oligosaccharides

A de novo synthetic method towards apiose, a structurally unusual furanose, is reported. The key feature is sequential metal catalysis consisting of the palladium‐catalyzed asymmetric intermolecular hydroalkoxylation of an alkoxyallene and subsequent ring‐closing metathesis (RCM). This strategy enabled the efficient synthesis of various apiose‐containing disaccharides and a unique convergent synthesis of trisaccharides.     

苯并呋喃类N-肉豆蔻酰基转移酶抑制剂的三维定量构效关系研究

摘要采用比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA), 系统地研究了40个苯并呋喃类N-肉豆蔻酰基转移酶(NMT)抑制剂的三维定量构效关系. 在CoMFA研究中, 考察了网格点步长对模型统计结果的影响. 在CoMSIA研究中, 研究了各种分子场组合、 网格点步长和衰减因子对模型统计结果的影响, 发现立体场、 静电场、 疏水场和氢键受体场的组合可得到最佳模型. 所建立的CoMFA和CoMSIA模型的交叉相关系数q2值分别为0.759和0.730, 均具有较强的预测能力. 利用CoMFA和CoMSIA模型的三维等值线图直观地解释了化合物的构效关系, 阐明了化合物结构中苯并呋喃环上各位置取代基对抑酶活性的影响, 为进一步结构优化提供了重要依据.     

Vitamin K2 as a New Modulator of the Ceramide De Novo Synthesis Pathway

The aim of the study was to evaluate the influence of vitamin K2 (VK2) supplementation on the sphingolipid metabolism pathway in palmitate-induced insulin resistant hepatocytes. The study was carried out on human hepatocellular carcinoma cells (HepG2) incubated with VK2 and/or palmitic acid (PA). The concentrations of sphingolipids were measured by high-performance liquid chromatography. The expression of enzymes from the sphingolipid pathway was assessed by Western blotting. The same technique was used in order to determine changes in the expression of the proteins from the insulin signaling pathway in the cells. Simultaneous incubation of HepG2 cells with palmitate and VK2 elevated accumulation of sphinganine and ceramide with increased expression of enzymes from the ceramide de novo synthesis pathway. HepG2 treatment with palmitate and VK2 significantly decreased the insulin-stimulated expression ratio of insulin signaling proteins. Moreover, we observed that the presence of PA w VK2 increased fatty acid transport protein 2 expression. Our study showed that VK2 activated the ceramide de novo synthesis pathway, which was confirmed by the increase in enzymes expression. VK2 also intensified fatty acid uptake, ensuring substrates for sphingolipid synthesis through the de novo pathway. Furthermore, increased concentration of sphingolipids, mainly sphinganine, inhibited insulin pathway proteins phosphorylation, increasing insulin resistance development.     

De Novo Synthesis of Highly Functionalized Benzimidazolones and Benzoxazolones through an Electrochemical Dehydrogenative Cyclization Cascade

Benzimidazolone and benzoxazolone moieties are important scaffolds in a variety of pharmaceutical molecules. These bicyclic heterocycles are usually prepared from a benzene derivative through the construction of an additional five‐membered heterocyclic ring. We report herein a method that enables the efficient synthesis of highly substituted benzimidazolone and benzoxazolone derivatives by building both the benzene and the heterocyclic rings through a dehydrogenative cyclization cascade. Readily available arylamine‐tethered 1,5‐enynes undergo a biscyclization/dehydrogenation cascade to afford functionalized benzanellated heterocycles in a single step with complete control of regioselectivity. These electricity‐powered oxidative transformations proceed with H₂ evolution, thus obviating the need for transition‐metal‐based catalysts and oxidizing reagents.     

Synthesis of Benzofuran Derivatives via Different Methods

This review presents a systematic and comprehensive survey of the methods of preparation of benzofurans. These compounds are important intermediates for the synthesis of a variety of synthetically useful and novel heterocyclic systems.     

De Novo Design of Functional Oligonucleotides with Acyclic Scaffolds

In this account, we demonstrate a new methodology for the de novo design of functional oligonucleotides with the acyclic scaffolds threoninol and serinol. Four functional motifs—wedge, interstrand‐wedge, dimer, and cluster—have been prepared from natural DNA or RNA and functional base surrogates prepared from d ‐threoninol. The following applications of these motifs are described: (1) photoregulation of formation and dissociation of a DNA duplex modified with azobenzene, (2) sequence‐specific detection of DNA using a fluorescent probe, (3) formation of fluorophore assemblies that mimic quantum dots, (4) improved strand selectivity of siRNA modified with a base surrogate, and (5) in vivo tracing of the RNAi pathway. Finally, we introduce artificial nucleic acids (XNAs) prepared from d ‐threoninol and serinol functionalized with each of the four nucleobases, which have unique properties compared with other acyclic XNAs. Functional oligonucleotides designed from acyclic scaffolds will be powerful tools for both DNA nanotechnology and biotechnology.