Synthesis of Spirocyclic and Fused Isoxazoline Building Blocks

A highly efficient multigram synthesis of spirocyclic and fused isoxazoline building blocks is described. Isoxazoline-3-carboxylates were synthesized via a regioselective 1,3-dipolar cycloaddition reaction of 2-chloro-2-(hydroxyimino)acetate and carbo- or heterocyclic alkenes bearing endo- or exocyclic C=C double bonds, resulting in fused or spirocyclic isoxazolines, respectively. The preparation of up to 300 g of these compounds was achieved in a single run. The ester group of isoxazolines was then subjected to common synthetic transformations for the synthesis of corresponding building blocks, including alcohols, chlorides, azides, amines, aldehydes, carboxylic acids, amino acids and their derivatives, difluoromethyl-substituted compounds, and bicyclic γ-lactones. Additionally, a direct cycloaddition-based approach to the synthesis of aminoalkyl- and chloromethyl-substituted isoxazolines was proposed to improve their preparation. The described isoxazoline building blocks are expected to be valuable tools for drug discovery.     

Aldo‐X Bifunctional Building Blocks for the Synthesis of Heterocycles

Compounds containing oxygen, nitrogen, or sulfur atoms inside the rings are attracting much attention and interest due to their biological importance. In recent years, several methods for the synthesis of such molecules have been reported by using aldo‐X bifunctional building blocks (AXB3 s) as substrates; these are a wide class of organic molecules that contain at least two reactive sites, among them, one aldehyde, acetal, or semiacetal group was involved. Because of the multiple reactivities, AXB3 s are widely used in the one‐pot synthesis of biologically important heterocycles. This review summarizes the synthesis of important heterocycles by using AXB3 s as pivotal components in establishing multicomponent reactions, tandem reactions, and so forth. In many cases, the established reaction systems with AXB3 s were characterized by some green properties, such as easy access to the substrate, mild and environmentally benign conditions, and wide scope of the substrate.     

Synthesis of Orthorhombic Mo‐V‐Sb Oxide Species by Assembly of Pentagonal Mo6O21 Polyoxometalate Building Blocks

Mix and match : The pentagonal [Mo₆O₂₁]^n? polyoxomolybdate building block assembles with other sources of Mo, V, and Sb ions to form an orthorhombic Mo‐V‐Sb oxide. The first single‐crystal X‐ray analysis of an orthorhombic Mo–V‐based oxide, a promising catalyst for light alkane selective oxidation known as the “M1 phase”, revealed the structure of the compound.

     

由D-Erythorbic Acid合成新的多官能团C4手性筑块

手性C4筑块是合成许多天然产物 Leukotrienes, Pyrrolizidine alkaloids及前列腺素A2等的重要合成子[1～3]. 然而到目前为止, 手性C4筑块只有从少数几种手性源如酒石酸, L-苏糖, D-赤藓糖等中才能得到[2～7]. 我们在以D-erythorbic acid为原料合成新型手性配体的过程中[8～10], 发现了一种简便获得选择性保护的多官能团手性C4筑块(化合物4, 5)的新途径(Scheme 1).     

3-Fluoroalkyl (CF3, CHF2, CH2F) Cyclobutane-Derived Building Blocks for Medicinal Chemistry: Synthesis and Physicochemical Properties

Synthesis and physicochemical characterization of all possible cis- and trans-1,3-disubstituted cyclobutane-derived amines and carboxylic acids bearing mono-, di- and trifluoromethyl groups at the C-3 position is disclosed. Tetramethylammonium fluoride (TMAF)- or morpholinosulfur trifluoride (Morph-DAST)-mediated nucleophilic fluorination of appropriate cis- and trans-diastereomeric substrates was used as the key step for the preparation of CH₂F- and CHF₂-substituted derivatives. To obtain the corresponding cis- and trans-isomeric CF₃-substituted derivatives, resolution of known 3-(trifluoromethyl)cyclobutanecarboxylic acid (obtained as a mixture of diastereomers) was applied. The proposed procedures were suitable for the preparation of corresponding fluoroalkyl-substituted cyclobutane-derived amines and carboxylic acids on up to 50 g scale. All 12 building blocks obtained were characterized by measuring dissociation constants (pK_a) and lipophilicities (LogP, for model derivatives) to evaluate the effect of the fluoroalkyl substituents on their physicochemical properties relevant to further drug discovery applications.     

Conjugated Oligothiophene Derivatives Based on Bithiophene with Unsaturated Bonds as Building Blocks for Solution‐Processed Bulk Heterojunction Organic Solar Cells

A new building block ATVTA that uses stiff carbon–carbon triple bonds (A) on 1,2‐di(2‐thienyl)‐ethene (TVT) has been developed. Oligothiophene derivatives S‐01 with a TVT unit, S‐02 with a 5,5′‐diethynyl‐2,2′‐dithienyl (AT2) unit and S‐03 with ATVTA were synthesized to compare their effects in a systematic study. Due to the better π‐conjugation extension of the TVT unit, S‐01 exhibits the most red‐shifted absorption profile among them, whereas S‐02 possesses the deepest HOMO level. While the HOMO level of S‐03 is down‐shifted by 0.02 eV relative to that of S‐01 , the alkyne linkages can effectively down‐shift the HOMO level. By replacing the terminal units of S‐03 with stronger electron acceptors, S‐04 and S‐05 exhibited broader absorption profiles and lower HOMO levels than those of S‐03 . Organic solar cells based on these molecules were fabricated and an S‐03 :PC₆₀BM (1:1, w/w) based device afforded the highest V_oc value of 0.96 V and a power conversion efficiency (PCE) of 2.19 %.     

酰胺电子等排体在先导化合物优化中的应用

生物电子等排体是指一类化合物或基团,这类物质拥有近似的分子形状和体积,类似的电子分布,并由此表现出相似的物理特性。作为激动剂或拮抗剂生物电子等排体能对相同的生化相关体系发挥作用,产生彼此互相相关的生物特性。药物结构中酰胺结构作为药效团和药物的重要组成部分被广泛应用。然而作为药物分子结构的重要组成部分,酰胺结构也存在着一些明显的缺点,包括代谢不稳定、代谢产物有毒和膜渗透性差等。为了克服这些缺点同时又想保持部分酰胺的特性,生物电子等排体替换是有效的方法之一。在先导化合物的优化过程中,通过酰胺生物电子等排体替换还能达到提高生物活性和靶点选择性、降低合成难度、扩展或突破知识产权限制等目的。本综述着重介绍了近五年来酰胺及其生物电子等排体在先导化合物优化过程中的应用。希望能对含有酰胺结构的先导化合物的优化提供新的思路,加速新药研发进程。     

Synthesis of N-Difluoromethyl Carbonyl Compounds from N-Difluoromethylcarbamoyl Fluorides

Fluorinated small molecules are commonly used in functional small-molecule chemistry, and N-difluoromethyl (N-CF₂H) compounds are particularly intriguing due to their unique and unexplored physiochemical properties. However, despite limited progress, a general methodological approach to the synthesis of N-CF₂H compounds remains elusive. Here, guided by computation, we present a simple and practical protocol to access N-CF₂H amides and related carbonyl derivatives. The protocol involves a one-pot conversion of thioformamides through desulfurization-fluorination and acylation, providing N-difluoromethylcarbamoyl fluoride building blocks that can be further diversified to a variety of unexplored N-CF₂H carbonyl compounds with rich functionality. Additionally, preliminary studies on their properties and stability showcased their potential application in pharmaceuticals and agrochemicals.     

一类新的多功能构筑基块-多吡唑化合物的设计合成

The design and synthesis of novel polypyrazolyl aromatic bridging ligands 1,3,5-tris（3,5-dimethyl-1-pyrazol-4-yl）benzene and 2,4,6-tris（4-（3,5-dimethyl-^1H-pyrazol-4-yl）phenyl）-1,3,5-triazine from simple starting materials mesitylene and p-tolunitrile were reported.     

Playing with Structures at the Nanoscale: Designing Catalysts by Manipulation of Clusters and Nanocrystals as Building Blocks

The purpose of this Concept is to highlight some of the most recent and promising methods for the preparation of tailored catalysts by designing and preparing the component building blocks and by assembling them in a controlled fashion. We want to emphasize how rational design and synthesis of catalysts must be coupled to precise catalytic and structural characterization of the systems in an ideal feedback loop. New catalyst design and preparation techniques, dictated by information about the active sites that the specific application requires, are frequently available. The building blocks for developing these novel catalysts include colloidal methods for the preparation of uniform nanostructures, physical methods for rational assembly of the building blocks (Langmuir–Blodgett, liquid–air self‐assembly), and development of rational interactions between the building blocks for enhanced activity of the assemblies. These methods, which apply techniques normally used in other fields of nanotechnology to catalysis, offer exciting opportunities to help improve currently available catalytic systems in terms of activity, stability and selectivity.     

Tetraindole Derivatives of Porphyrins as Building Blocks in the Synthesis of Monodisperse Polyphenols

A new strategy for the synthesis of monodisperse polyphenols chemically bound to a rigid thermally stable molecular platform has been suggested. The platform has been prepared by the Suzuki–Miyaura reaction of a tetraboryl porphyrin derivative and 3-(4′-bromophenyl)-4,6-dimethoxyindole. Subsequent reactions of complete demethylation of obtained tetraindole and partial blocking of the corresponding phenolic hydroxyls by acid-labile protective groups have led to the formation of a final modified polyphenol compound of the porphyrin series. On the basis of the this polyphenol, a positive photoresist for lithography with exposure radiation at a wavelength of 13.5 nm has been developed; the photoresist affords the fabrication of topological structures with 16-nm resolution.     

C,N-Diarylformamidines as Valuable Building Blocks in the Synthesis of Heterocyclic Compounds

Obtaining highly functionalized heterocyclic structures is an important topic of modern organic synthesis, as it reveals the possibility of constructing more complex systems and therefore, expanding the range of various drugs. Aiming at synthesizing complex molecules from simple and readily available reagents, the modification of C,N-diarylformamidines, well known in medicinal chemistry, is of great interest. This article reviews comprehensively the field of C,N-diarylformamidine chemistry and covers publications on this topic from 1999 to 2022.     

由杂多酸衍生物制备溶致液晶

液晶是介于液态和晶态之间的一个独立的物质状态,溶致液晶是因溶质在一定浓度范围内分散在溶剂中而呈液晶相．自从１８８８年奥地利植物学家Ｒｅｉｎｉｔｉｚｅｒ和德国物理学家Ｌｅｈｍａｎｎ合作首次发现液晶态以来［１］,迄今为止己发现了五万种以上的液晶性物质．它...     

Tailor‐Made Metal–Organic Frameworks from Functionalized Molecular Building Blocks and Length‐Adjustable Organic Linkers by Stepwise Synthesis

In this work, we have demonstrated a family of diamondoid metal–organic frameworks (MOFs) based on functionalized molecular building blocks and length‐adjustable organic linkers by using a stepwise synthesis strategy. We have successfully achieved not only “design” and “control” to synthesize MOFs, but also the functionalization of both secondary building units (SBUs) and organic linkers in the same MOF for the first time. Furthermore, the results of N₂ and H₂ adsorption show that their surface areas and hydrogen uptake capacities are determined by the most optimal combination of functional groups from SBUs and organic linkers, interpenetration, and free volume in this system. A member of this series, DMOF‐6 exhibits the highest surface area and H₂ adsorption capacity among this family of MOFs.     

Hybrid Siloxane-Based Nano Building Blocks for Optical Applications: Optimization of the Synthetic Procedures by Spectroscopic Analysis

Diphenylsilanediol (DPDO) reacts with triethoxysilane (TREOS) in anhydrous conditions and in the presence of pyridine, to form complex mixtures of linear and cyclic condensation products which were identified by ²⁹Si NMR and ATR/FTIR spectroscopies. The distribution of products can be varied by modifying the reaction conditions. Spectroscopic analysis allowed to identify the optimal reagents ratio and concentration for the production of hetero-condensation products minimizing the number of residual –OH groups whose presence would affect the performance of optical waveguides based on the synthesised nano building blocks.