Organocatalysis mediated by (thio)urea derivatives

Over the last decade the potential for N,N-dialkyl(thio)urea derivatives to serve as active metal-free organocatalysts for a wide range of synthetically useful reactions susceptible to the influence of general acid catalysis has begun to be realised. This article charts the development of these catalysts (with emphasis on the design principles involved), from early "proof-of-concept" materials to contemporary active chiral (bifunctional) promoters of highly selective asymmetric transformations.     

Atom-economy Synthesis of N-Substituted Carbamate from Urea Derivative and Dimethyl Carbonate Catalyzed by La/SiO_2: Characterization and Activity

A series of silica gel immobilized lanthanum catalysts were prepared for the atom‐economy synthesis of N‐substituted carbamates from urea derivatives and dimethyl carbonate. The La/SiO₂ catalysts with lanthanum loadings varied from 1.3 wt% to 8.5 wt% were characterized by AES, BET, XRD, TEM, FT‐IR, XPS and TPD. According to the characterization, lanthanum species with particle sizes of 5–10 nm on the surface of silica gel were formed. The catalysts were all amorphous and the surface areas were 336.5–530.2 m²/g. NH₃‐TPD analysis showed that all samples exhibited similar acid strength with different acid amounts. FT‐IR measurement indicated that the component of lanthanum species on the catalyst surface were La(OH)₃, LaOOH and hydrated La₂O₃. Also, the peak value of the absolute amount of LaOOH was obtained with 4.3 wt% lanthanum loading. The BET surface area decreased dramatically when the lanthanum loading was above 4.3 wt%. In consideration of the results obtained from the catalytic reactions, it could be concluded that LaOOH was the possible active species and high surface area was important for the high catalytic activity.     

Three Component Reaction: An Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones and Thiones Using Heterogeneous Catalyst

Fluoroboric acid supported on silica gel (HBF₄‐SiO₂) catalyzes efficiently the three component condensation of an aldehyde, a 1,3‐dicarbonyl compound and urea or thiourea to afford the corresponding 3,4‐dihydropyrimidin‐ 2(1H)‐ones and thiones in high yields. The ambient conditions, fast reaction rates, and excellent product yields are the important characteristics of this reaction.     

非对称取代脲的合成与应用

总结了合成非对称取代脲的几种方法，分析了各种方法的利弊，介绍了非对称 取代脲的主要应用，指出直接利用一氧化碳进行硒催化的胺与硝基化合物的氧化还 原羰基化反应来合成非对称取代脲的方法是比较有发展前景的方法，并对硒催化的 氧化还原羰基化反应作了较为详细的介绍。     

Radical Anions from Urea‐type Carbonyls: Radical Cyclizations and Cyclization Cascades

Radical anions generated from urea carbonyls by reductive electron transfer are exploited in carbon–carbon bond formation. New radical cyclizations of urea radical anions deliver complex nitrogen heterocycles and, depending upon the proton source used in the reactions, a chemoselective switch between reaction pathways can deliver two heterobicyclic scaffolds. A computational study has been used to investigate the selectivity of the urea radical processes. Furthermore, radical cyclization cascades involving urea radical anions deliver unusual spirocyclic aminal architectures.     

Anion-Coordination-Assisted Assembly of Supramolecular Charge-Transfer Complexes Based on Tris(urea) Ligands

Charge-transfer (CT) complexes, formed by noncovalent bonding between electron-rich (donor, D) and electron-deficient (acceptor, A) molecules (or moieties) have attracted considerable attention due to their fascinating structures and potential applications. Herein, we demonstrate that anion coordination is a promising strategy to promote CT complex formation between anion-binding, electron-rich tris(urea) donor ligands (D) and electron-deficient viologen cation acceptors (A), which form co-crystals featuring infinite ⋅⋅⋅DADA⋅⋅⋅ or discrete (circular DADA or three-decker DAD) π-stacking interactions. These CT complexes were studied by X-ray diffraction, UV/Vis spectroscopy, electric conductivity measurements, charge displacement curve (CDC) calculations, and DFT computations.     

Manganese-Modulated Cobalt-Based Layered Double Hydroxide Grown on Nickel Foam with 1D–2D–3D Heterostructure for Highly Efficient Oxygen Evolution Reaction and Urea Oxidation Reaction

Hydrogen production by energy-efficient water electrolysis is a green avenue for the development of contemporary society. However, the oxygen evolution reaction (OER) and the urea oxidation reaction (UOR) occurring at the anode are impeded by the sluggish reaction kinetics during the water-splitting process. Consequently, it is promising to develop bifunctional anodic electrocatalysts consisting of nonprecious metals. Herein, a bifunctional CoMn layered double hydroxide (LDH) was grown on nickel foam (NF) with a 1D–2D–3D hierarchical structure for efficient OER and UOR performance in alkaline solution. Owing to the significant synergistic effect of Mn doping and heterostructure engineering, the obtained Co₁Mn₁ LDH/NF exhibits satisfactory OER activity with a low potential of 1.515 V to attain 10 mA cm⁻². Besides, the potential of the Co₁Mn₁ LDH/NF catalyst for UOR at the same current density is only 1.326 V, which is much lower than those of its counterparts and most reported electrocatalysts. An urea electrolytic cell with a Co₁Mn₁ LDH/NF anode and a Pt–C/NF cathode was established, and a low cell voltage of 1.354 V at 10 mA cm⁻² was acquired. The optimized strategy may result in promising candidates for developing a new generation of bifunctional electrocatalysts for clean energy production.     

Photocatalytic Difunctionalization of Vinyl Ureas by Radical Addition Polar Truce–Smiles Rearrangement Cascades

We report tandem alkyl-arylations and phosphonyl-arylations of vinyl ureas by way of a photocatalytic radical-polar crossover mechanism. Addition of photoredox-generated radicals to the alkene forms a new C−C or C−P bond and generates a product radical adjacent to the urea function. Reductive termination of the photocatalytic cycle generates an anion that undergoes a polar Truce–Smiles rearrangement, forming a C−C bond. The reaction is successful with a range of α-fluorinated alkyl sodium sulfinate salts and diarylphosphine oxides as radical precursors, and the conformationally accelerated Truce–Smiles rearrangement is not restricted by the electronic nature of the migrating aromatic ring. Formally the reaction constitutes an α,β-difuctionalisation of a carbon–carbon double bond, and proceeds under mild conditions with visible light and a readily available organic photocatalyst. The products are α,α-diaryl alkylureas typically functionalized with F or P substituents that may be readily converted into α,α-diaryl alkylamines.     

Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer

The enzyme soluble epoxide hydrolase (sEH) plays a central role in metabolism of bioactive lipid signaling molecules. The substrate-specific hydrolase activity of sEH converts epoxyeicosatrienoic acids (EETs) to less bioactive dihydroxyeicosatrienoic acids. EETs exhibit anti-inflammatory, analgesic, antihypertensive, cardio-protective and organ-protective properties. Accordingly, sEH inhibition is a promising therapeutic strategy for addressing a variety of diseases. In this review, we describe small molecule architectures that have been commonly deployed as sEH inhibitors with respect to angiogenesis, inflammation and cancer. We juxtapose commonly used synthetic scaffolds and natural products within the paradigm of a multitarget approach for addressing inflammation and inflammation induced carcinogenesis. Structural insights from the inhibitor complexes and novel strategies for development of sEH-based multitarget inhibitors are also presented. While sEH inhibition is likely to suppress inflammation-induced carcinogenesis, it can also lead to enhanced angiogenesis via increased EET concentrations. In this regard, sEH inhibitors in combination chemotherapy are described. Urea and amide-based architectures feature prominently across multitarget inhibition and combination chemotherapy applications of sEH inhibitors.     

荧光猝灭法和动态光散射法研究尿素-水混合溶剂中牛血清白蛋白的构象变化

利用荧光猝灭法和动态光散射法测定尿素-水混合溶剂中牛血清白蛋白(BSA)与荧光素的结合距离和BSA的流体动力学半径, 并通过分析BSA和荧光素在BSA-尿素-水和荧光素-尿素-水三元体系以及BSA-荧光素-尿素-水四元体系中荧光光谱的变化, 探讨尿素与蛋白质分子在水溶液中相互作用的机理及其对蛋白质构象的影响. 结果显示, BSA的3个结构域在尿素-水混合溶剂中具有不同的稳定性, 其中结构域III在尿素-水混合溶剂中是不稳定的, 而结构域I和结构域II分别在尿素浓度大于3.0和4.0 mol•L－1的混合溶剂中发生去折叠. 试验发现, BSA结构域II在低于去折叠浓度的尿素-水混合溶剂中形成更为紧密的构象, 这一现象可以归因于尿素与BSA结合引起的“蛋白质粘稠效应”