Chinese Journal of Organic Chemistry-Forthcoming Articles

Research progress on enantioselective desymmetrization reactions involving metal carbenes

Teng Ming-Yu, Han Tao, Huang En-He, Ye Long-Wu

Metal carbenes have been widely applied in organic synthesis, and they can undergo a variety of chemical transformations due to their versatile reactivities. In this review, the desymmetrization of C-H insertion reaction, Buchner reaction, Si-H insertion reaction and B-H insertion reaction involving metal carbenes is introduced according to the different reaction types of metal carbenes. Under the catalysis of chiral rhodium, ruthenium and copper catalysts, chiral carbocycles, heterocycles, organosilicons and organoborons can be obtained with high enantioselectivity, which greatly enriches the development of asymmetric synthetic chemistry.

Transition Metal-Catalyzed Asymmetric Cyclizations with Allyl or Propargyl Heteroatom-Dipole Precursors

Zhang Jian, Chen Ying, Wang Quannan, Shen Jiahuan, Liu Yangzi, Deng Weiping

Chiral heterocyclic compounds are an important class of chiral substances, which are widespread in many chiral drugs, pesticides and catalysts. Therefore, the efficient asymmetric synthesis of the above compounds becomes a research hotspot in organic synthesis. Transition metal-catalyzed asymmetric cyclization with heteroatom-dipole precursors is an important method to construct these frameworks. Among them, the heteroatom-dipole precursors designed based on transition metal-catalyzed allyl or propargyl substitutions have been extensively studied in the past two decades and occupied an important role in this field. In this paper, the transition metal-catalyzed asymmetric cyclization with allyl or propargyl heteroatom-dipole precursors are introduced in detail. The advantages and existing problems of the current methods are analyzed, which would provide useful reference for the researchers in asymmetric synthesis and related fields.

Addition of Benzyne to 2-Hydroxypyrimidine to Synthesize 2-Aryloxypyrimidine Derivatives under Mild Conditions

Wang Wenpeng, Yang Chunhong, Liu Haichao, Wang Xicun, Quan, Zhengjun

Pyrimidine aryl ether derivatives have attracted widespread attention from chemists for their diverse biological activity and pharmacological properties. In this paper, a series of pyrimidine-2-arylethers derivative were synthesized with moderate to good yield by using 2-(trimethylsilyl)phenyl trifluoromethanesulfonate as a source of benzyne to react with 2-hydroxypyrimidine. Compared with the traditional method, this method has the advantages of transition-metal-free, easy preparation of 2-aryloxypyrimidine derivatives, wide functional group compatibility and high yield.

Synthesis and Antiproliferative Activity of Novel 2,4,6-Trisubstituted Pyrimidine Derivatives

In order to find new and efficient anti-tumor drugs, a series of 2,4,6-trisubstituted pyrimidine derivatives were designed and synthesized, and evaluated for antiproliferative activity against four cancer cell lines of PC-3, MGC-803, MCF-7 and HGC-27 using methyl thiazolyl tetrazolium (MTT) assay. The results showed that most of the compounds exhibited moderate to potent antiproliferative activity against the four human tumor cell lines, among which compound N-(3-(2-((4-((1,3,4-thiadiazol-2-yl)thio)-6-(Trifluoromethyl)pyrimidin-2-yl)thio)acetamido)phenyl)acrylamide (19q) had the best inhibitory activity against PC-3 cells, with IC₅₀ value of (0.87 ± 0.15) μmol·L^-1, the antitumor activity was significantly better than the positive control 5-Fluorouracil. Further anti-tumor mechanism studies showed that compound 19q can induce apoptosis in PC-3 cells. In addition, compound 19q might play an anti-tumor effect by down-regulating the expression of anti-apoptotic protein Bcl-2 and up-regulating the expression of pro-apoptotic proteins Bax and p53.

Modular Access to Esterified/Fused Isocoumarins via Rh-catalyzed C-H Activation/Transannulative Coupling /Annulation of Phthalic Anhydrides with Cyclic 2-Diazo-1,3-diketones and Methanol

Shang Mingzhou, Zhang Lanlan, Chen Miaomiao, Hu Wangcheng, He Xinwei

A rhodium(III)-catalyzed cascade reaction of phthalic anhydrides with cyclic 2-diazo-1,3-diketones and methanol for modular access to esterified cyclohexenone-fused isocoumarins has been developed. This strategy involves the process of one C-C and two C-O bonds formation through C-H activation, transannulative coupling, and subsequent annulation process. Furthermore, no additive and base are needed in this transformation, and interestingly, the reaction could proceed well under air atmosphere with broad substrate and good functional groups tolerance.

Synthesis of polysubstituted 2,3-dihydrofurans via P(NMe₂)₃-mediated [1+4] annulation of 1,2-dicarbonyl compounds with α, β-unsaturated ketones

Feixue Xue, Jianwei Zeng, Taishan Yan, Jie Han, Zhengjie He

Herein a [1+4] annulation of 1,2-dicarbonyl compounds with α, β-unsaturated ketones has been readily realized under the mediation of P(NMe₂)₃, producing polysubstituted 2,3-dihydrofurans bearing a quaternary carbon center in fair to good yields with a broad substrate scope. This reaction accordingly constitutes a new synthetic method for such compounds. In some cases, a [1+2] annulation reaction competitively occurs, delivering polysubstituted cyclopropanes. With the aid of DFT calculation, a plausible mechanism for the [1+4] annulation and the chemoselectivity between [1+2] and [1+4] annulations has been discussed.

Selective Epoxidation of β-Ionone Catalyzed by Iron-Doped Se/C

Hongen Cao, Peizi Li, Xiaobi Jing, Hongwei Zhou

As an important intermediate in pharmaceutical synthesis, 5,6-epoxy-β-ionone has unique industrial application value. Recently, we have designed and prepared an iron-doped Se/C catalyst by calcining a mixture of methylselenized glucose with FeCl₃. The material could activate the molecular oxygen to achieve the selective epoxidation of β-ionone affording 5,6-epoxy-β-ionone. The catalyst is stable and recyclable, and the catalytic reaction process did not require any additive, so that the production cost could be obviously reduced. This cheap and safe catalytic oxidation technology using molecular oxygen as oxidant is of good industrial application values.

Difluorinated Silyl Enol Ethers as Fluorine-Containing Building Blocks for the Synthesis of Organofluorine Compounds

Organofluorine compounds have been widely applied in various fields ranging from drug discovery, clinical medicines, agrochemistry, and materials science to organic synthesis, due to their special chemical and physical properties when compared with nonfluorinated analogs. In the past decades, significant progress has been made in the development of selective fluorination and fluoroalkylation for the synthesis of structurally diverse fluorine-containing molecules. Among them, the α-fluoroalkylated carbonyl group represents an important class of scaffold components in biologically active and druglike compounds. In this context, based on the use of difluorinated silyl enol ether (DFSEE) as a unique fluoroaklylating reagent, a variety of methods for the incorporation of gem-difluoroalkylated carbonyl moiety have been achieved, including aldol, Mannich, arylation, allylation, protonation, halogenation, conjugate addition, and olefination reactions. On the other hand, DFSEEs could also merge with new types of reactions such as radical-type difluoroalkylation and cascade reaction by virtue of their incredible reactive flexibility. In addition, the O-site selective addition of DFSEEs was also reported, enabling the construction of versatile gem-difluoroalkenes. Given the importance of organofluorine compounds and the synthetic potential of these avenues, herein, we highlight the recent advances in the functionalization of gem-difluorinated silyl enol ethers, which serve as key fluorine-containing building blocks for the synthesis of organofluorine compounds.

Synthesis, Antifungal Activity and Molecular Docking Study of 1, 3, 4-Thiadiazole-Urea Compounds Containing gem-Dimethylcyclopropane Ring Structure

In an attempt to search for natural renewable product-based antifungal agents, eighteen 1, 3, 4-thiadiazole-urea compounds containing gem-dimethylcyclopropane ring structure were designed and synthesized. Their structures were confirmed by FT-IR, ¹H NMR, ¹³C NMR, ESI-MS, and elemental analysis. The antifungal activity of the target compounds against six plant pathogens was preliminarily evaluated, at the concentration of 50 mg/mL. As a result, the inhibitory rates of compound 7i (R = p-Br) against Colletotrichum orbicular, Bipolaris maydis, and Alternaria solani were 91.2%, 85.0%, and 60.1%, respectively, better than that of the positive control chlorothalonil. Furthermore, a reasonable and effective 3D-QSAR model (r² = 0.990, q² = 0.517) was established by the comparative molecular field analysis method (CoMFA). The binding mode between the target compounds and succinate dehydrogenase (SDH) was investigated by molecular docking, and the cation-π interaction between the key residue Arg and the benzene ring was quantitatively analyzed. The gem-dimethylcyclopropane and thiadiazole-urea-benzene moieties of the target compounds probably made major contributions to the antifungal activity by frontier molecular orbital calculation.

Design and synthesis of novel aggregation-induced luminescence molecules based on isoquinoline

Tan Jiamin, Yu Yajun, Guan Meng, Zhao Yunhui, Tang Zilong, Zhou Zhihua, Guo Tao

Aggregation induced emission (AIE) molecules have been widely used in chemistry, biosensor, cell imaging and OLED due to their excellent spectral properties. In this study, it was found for the first time that isoquinoline benzoxazine molecules exhibited good fluorescent emission in a high proportion of water/acetonitrile mixed solution, showing an obvious AIE phenomenon. On this basis, a novel type of AIE molecules fused with tetraphenylene and isoquinoline structural units were designed and synthesized. They were found exhibiting an excellent AIE phenomenon. It was confirmed by density functional theory (DFT) calculations that the splicing of the two structural units effectively reduced the energy gap of the frontier orbitals, which was helpful for the preparation of fluorescent molecules with longer emission wavelengths. In this study, AIE molecules based on the isoquinoline structure were discovered and prepared, which enriched the members of the AIE family. The AIE molecules based on the isoquinoline structure were first discovered and prepared in this study, which enriched the members of the AIE family.

PhSO₃CH₂F：A New Reagent for O-Monofluoromethylation of Acetylacetone Derivatives

Li Shan, Jiang Lvqi

A new shelf-stable and easily scalable monofluoromethylating reagent fluoromethyl benzenesulfonate (PhSO₃CH₂F) was developed. This reagent is able to react with acetylacetone derivatives to afford corresponding O-monofluoromethylated products in high selectivity and good yields under mild conditions. Moreover, the method could be used in late-stage monofluoromethylation. This method provides more options for the synthesis of monofluoromethyl compounds

Recent Advances in Ni-Catalyzed Asymmetric Reductive Difunctionalization of Alkenes

Yuanyuan Ping, Haixia Song, Wangqing Kong

Alkenes are cheap and easily available bulk industrial feedstocks. Difunctionalization of alkenes can rapidly construct complex molecules, which have broad applications in organic synthesis. Compared with traditional redox-neutral alkene difunctionalization, the reductive difunctionalization of alkenes can introduce two different electrophiles to both sides of the carbon-carbon double bond, which has the advantages of mild reaction conditions, high functional group tolerance, and no need for pre-prepared organometallic reagents. This review summarizes the latest research progress in nickel-catalyzed reductive difunctionalization of alkenes. The development prospect of the reaction is prospected.

I₂-Catalyzed Oxidative Coupling of 2-Aminopyridines with N-tosylhydrazones—Synthesis of 1,2,4-Triazolo[4,3-α]pyridines

Yongxin Chen, Xin Guo, Yafeng Liu, Xueying Yang, Baohua Chen

An efficient synthesis of 1,2,4-triazolo[4,3-α]pyridines from N-tosylhydrazones and 2-aminopyridines via S-N/C-N bond cleavage and new C-N bond formation has been developed. The procedure, using I₂ as the catalyst, is a simple, general, and efficient protocol, which could be applied to various substrates in moderate to good yields.

Recent Advances in Catalytic Asymmetric 1,3-Dipolar Cycloaddition Reactions with Kinetic Resolution

Liu Hua-Chao, Shen Chong, Chang Xin, Wang Chun-Jiang

Kinetic resolution is an efficient and widely used asymmetric organic synthesis strategy, which can transform racemic compounds into highly optically active building blocks. It is quite an important part of modern asymmetric synthesis. Although it has long been known as a common method to gain enantioenriched raw material, kinetic resolution processes involving asymmetric catalysis often show poor resolution efficiency and limited substrates scope in practice, which greatly hinder the development of this strategy. It is not until the past two decades, with the rapid development of chiral ligands and catalysts in the field of asymmetric catalysis, that kinetic resolution strategy has been increasingly applied in the efficient separation of racemic substrates to provide versatile chiral molecules with excellent optical purity. Since the strategy of kinetic resolution was first successfully employed in the catalytic asymmetric 1,3-dipolar cycloadditions with azomethine imines in 2005, studies on 1,3-dipolar cycloadditions with efficient kinetic resolution to achieve chiral N-heterocyclic compounds or highly enantioselective fragments have been well developed. The recent progress of kinetic resolution strategy in catalytic asymmetric 1,3-dipolar cycloaddition reactions involving azomethine imines and azomethine ylides is summarized according to the different azomethine 1,3-dipoles involved, and the related limitations and development prospects are also discussed.

Recent Advances in Visible-Light Photocatalytic Asymmetric Synthesis Enabled by Chiral Lewis Acids

Cheng Xiuliang, Li Dong, Yang Boxuan, Lin Yu-Mei, Gong Lei

In the past decade, visible-light photocatalytic asymmetric synthesis has shown considerable potential in the mild and rapid construction of optically active organic molecules with structural diversity. Chiral Lewis acids (CLA), including chiral borane compounds, lanthanum complexes, first-row transition metal complexes, and chiral-at-iridium or rhodium complexes, have been established as one class of the most effective catalysts being capable of controlling the stereochemistry in photo-induced chemical transformations. This review presents recent advances in this emerging field, in which the reactions are classified into bifunctional CLA photocatalytic reactions and reactions enabled by dual catalysis with a CLA catalyst and an external photosensitizer. We expect that these studies will stimulate progress in organic synthesis, photocatalysis and asymmetric catalysis.

Synthesis and Antitumor Activity Evaluation of 2,4,6-Trisubstituted Quinazoline Derivatives Containing Thiazole Structure

A series of 2,4,6-trisubstituted quinazoline derivatives containing thiazole group were designed and synthesized, and their antiproliferative activities against human tumor cell lines (PC-3,H1975,MGC-803 and A549)were determined. 3-((2-(((2-chlorothiazol-5-yl)methyl)thio)-6-methoxyquinazolin-4-yl)amino)benzonitrile(14i) was identified as the most potent compound in antiproliferation against MGC-803 cells, with the value was 4.54±0.32 μmol/L, which was better than the positive control 5-FU(8.14 ± 0.68 μmol/L). Further mechanistic studies showed that compound 14i could inhibit the clonal proliferation and migration of MGC-803 cells. In addition, compound 14i could induce apoptosis of MGC-803 cells and arrest the cell cycle at G2/M phase. These results indicated that compound 14i could as a potential antitumor drug.

Recent Advances in the Decarboxylative Acylation/Cyclization of α-Keto Acids

Wu Yechun, Yu Jin-Tao

Decarboxylation of α-keto acids is a simple and efficient method to obtain corresponding acyl radicals. Cascade radical cyclization has been proved as efficient approach towards cyclic structures, especially heterocyclic ones. A variety of acylated cyclic compounds such as indolones, quinolinones, phenanthridines, coumarins, chromones, benzothiophenes, and pyrrole[1,2-a]indoles could be constructed using α-keto acids via the decarboxylative acylation/cyclization with acyl radicals as intermediates. This review focused on the recent advances in the acylation/cyclization reaction triggered by acyl radicals that formed from the decarboxylation of α-keto acids.

Research Progress of Naphthalimide Derivative Optical Probes for Monitoring Physical and Chemical Properties of Microenvironment and Active Sulfur Substances

Naphthalimide derivatives have been designed as optical probes and applied in various biological scenarios due to their excellent photophysical properties. As an important microenvironment and active sulfur substance in biology plays an important role in biological system, it is necessary to detect it efficiently. The detection of naphthalimide derivatives for microenvironment and active sulfur substances is reviewed. The detection of microenvironment is described from four aspects of pH value, viscosity, polarity and temperature, and the design scheme of the probe and the comparison of all kinds of fluorescence properties are discussed. From the point of view of detection strategy, we divide the mechanism into nucleophilic substitution strategy, nucleophilic addition strategy, substituent reduction strategy, heavy metal replacement strategy and other strategies, and summarize and compare the fluorescence properties of these probes. Finally, some shortcomings in the design and practical application of this kind of probe are described, and the future prospect of this field is prospected.

Thia-Michael addition tandem reactions catalyzed by AlCl₃@MNPs

Ying Anguo, Bai Linsheng, Hou Hailiang, Xu Songlin, Liu Zhongqiu, Wang Limin

Magnetic nanoparticles (MNPs), prepared by co-precipitation method, were coated using hydrolysis of tetraethyl orthosilicate (TEOS) under basic conditions. The core-shell structured supporters were further grafted by AlCl₃ to obtain the finally catalyst AlCl₃@MNPs, which was fully characterized by X-Ray Photoelectron Spectroscopy (XPS), X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Scanning Electron Microscope (SEM) and Vibrating Sample Magnetometer (VSM), indicating the successful immobilization of AlCl₃ on the surface of the MNPs through coordination bond, and the magnetic nanoparticles supported aluminum chloride AlCl₃@MNPs was used in the thia-Michael addition tandem reactions. The as-prepared catalyst AlCl₃@MNPs promoted smoothly the reaction of amines, carbon disulfide and α,β-unsaturated carbonyl compounds to achieve good to excellent product yields of 59%-99%. Large surface area, excellent dispersion of catalyst in reaction solution and coordinative bond between AlCl₃ and hydroxyl cluster in MNPs ensure the highly catalytic efficiency. In addition, AlCl₃@MNPs can be readily recovered with external magnetic field and recycled for 10 times without significant loss of catalytic activity, demonstrating its advantage over the precursor AlCl₃ and excellent potential in industrial application.

Research progress on the synthesis of quercetin derivatives

Mao Yajun, Shao Xiangmin, Li Yangjie, Cao Ruimei, Feng Yali, Zhai Guangyu

Quercetin is a natural antioxidant, mainly found in vegetables, fruits and other plants. It can regulate many intracellular and extracellular signaling pathways related to disease progression. It can be anti-inflammatory, antiviral, anticancer, prevent and treat cardiovascular and cerebrovascular diseases, which has a wide range of pharmacological activities. Due to the structural characteristics of quercetin, its low bioavailability limits its clinical application. However, quercetin's low molecular mass and easily modifiable chemical groups make it attractive for drug development. Therefore, researchers have designed and synthesized new quercetin derivatives through various methods to improve its unfavorable factors, and then play a role in preventing and treating diseases. People modify the hydroxyl group of quercetin to introduce acyl groups, which increase the lipid solubility and improve bioavailability; introduce active groups to increase anti-inflammatory and antiviral activities; modify carbonyl group and replacing oxygen atom with sulfur or selenium, the anticancer activity was significantly enhanced ; complexes with metal ions, the biological activity was increased. Many quercetin derivatives with excellent properties, good solubility, high bioavailability, stable metabolism, low toxicity and significant biological activity have been synthesized by modifying quercetin through structural optimization.This paper reviews the recent progress in the synthesis of quercetin derivatives and their biological activities, and provides a reference for the further development of quercetin derivatives.

Construction of Quinazolin(thi)ones by Brønsted Acid/Visible-Light Photoredox Relay Catalysis

Pan Zhentao, Liu Tong, Ma Yongmin, Yan Jianbo, Wang Ya-Jun

A relay Brønsted acid/visible-light photoredox catalysis strategy for the synthesis of quinazolin(thi)ones is described. In this procedure, 2-aminoacetophenones and iso(thio)cyanates undergo Brønsted acid catalyzed [4+2] annulation, followed by photocatalyzed C-C bond cleavage reaction. A wide range of diversely substituted quinazoline-2,4-diones and quinazoline-2-thione-4-ones were synthesized under mild conditions. The protocol features eco-benign energy source and solvent, metal-free catalysts, simple starting materials and air as green oxidant.

Syntheses and Properties of Heteroatom-Doped Conjugated Nanohoops

Hui-Jun Zhang, Jianbin Lin

As structural models for carbon nanotube segments, radially conjugated carbon nanohoops have received much attention from chemists, which led to a series of bottom-up synthetic strategies. However, most of these nanohoops are composed only of benzene and simple polyaromatic hydrocarbon moieties. Modulation of the optoelectronic properties is mainly dependent on the variation of ring size, which greatly limits the functional development and application of conjugated nanohoops. In recent years, syntheses and property study of heteroatom-doped carbon nanohoops have become a new research hotspot. In this paper, we focus on the design, synthesis and properties of conjugated nanohoops involving heterocyclic subunits such as pyridine, thiophene, furan, carbazole, benzothiadiazole, chrysenylene, 1,2-azaborine heterocycle, diketopyrrolopyrrole, porphyrin, perylene diimide, and naphthodithiophene diimide, etc. Most of these nanohoops have special topological structures. The introduction of heteroatoms not only significantly improves their optoelectronic properties, but also regulates their assembly, leading to new skeletons for multifunctional supramolecular systems and organic materials.

Advances in the Catalytic Asymmetric Synthesis of Chiral Spiroketals

Yan Hui, Zhang Man, Li Lin, Hu Teng, Yang Wu-lin

As an unique spiro skeleton, spiroketals are ubiquitous motifs in many natural products, biologically active molecules, and privileged chiral ligands. The development of efficient synthetic methods for the preparation of spiroketals has long been a hot research topic in organic synthesis. In particular, the remarkable advances regarding the catalytic asymmetric synthesis of chiral spiroketals have been achieved over the past decade. This paper will summarize the progress in the field of catalytic asymmetric synthesis of chiral spiroketals according to the reaction types. The future development direction of this field is also prospected.

A Solvent-Regulated Dediazotized Oxygenation of α-Aryl α-Diazoesters and DDQ

Jia Run-Hong, Liu Shuai, Wang Shi-Chao, Hao Wen-Juan, Jiang Bo

A new metal-free, solvent-regulated dediazotized oxygenation of α-aryl α-diazo esters and DDQ is reported. The reaction of α-aryl α-diazo esters and DDQ in 2:1 mol ratio in DCM underwent double dediazotized O-H bond insertion reactions to access α,α’-(1,4-phenyldioxy)diesters as major products, whereas a series of structurally complex α,α-diaryloxy esters were provided with moderate to good yields when the reaction of these substrates in 3:2 mol ratio in DCE proceeded through a double dediazotized O-H bond insertion and dediazotized deoxygenation cascade. The controlled experiments confirmed that the hydrogen atom is from water during O-H bond insertion process. In addition, the reaction featured mild conditions, simple operation and controllable chemoselectivity without any catalyst.

Preparation of L-Lactide with High Optical Purity via the Zinc-Doped Polypyrrole-Catalyzed Lactic Acid Condensation

Xudong Cui, Xiangkun Meng, Ying Chen, Yonghong Liu, Lei Yu

As a biodegradable polymer, poly-lactic acid (PLA) has a wide application prospect. At present, high quality PLA is mainly produced via lactide condensation. In the technique, the optical purity of lactide is the key factor affecting the mechanical properties of produced PLA. Thus, developing the synthesis technology of lactide with high optical purity is a challenging subject with good application value. In this work, we designed and prepared zinc-doped polypyrrole (Zn@PPy) catalyst. The material could catalyze the condensation of LA to synthesize lactide with high optical purity. Notably, the material could be reused for many times and with the optical purity of the produced lactide over 98%.

Recent Advances in Transition Metal-Catalyzed Isocyanide Insertion Reactions

Gao, Qiushan, Li, Meng, Wu, Wanqing

As a class of small organic molecules containing (-NC) functional groups with high activity, isocyanide has been widely employed in organic synthesis, materials science, as well as coordination chemistry. In recent years, the transition metal-catalyzed isocyanide insertion reactions have attracted much attention due to the convenient and simple operations, the efficiency in the formation of diverse new bonds and good reaction selectivity. A series of highly useful chain or cyclic compounds have been successfully constructed using this strategy, such as functionalized ketones, amides, nitrogen heterocyclic compounds, etc. To study the most recent progress, we briefly summarize the advances in transition metal-catalyzed isocyanide insertion reactions since 2017 to 2021 according to different metal categories, and the future development has also been prospected in this review.

Constrution and Insecticidal Activities of Trifluoromethylated benzocyclicsulfoximine Derivatives by [3+2] Cycloaddition Reaction of Beznyne

Li, Wenjuan, Zhang, Rui, Cai, Zhihua, Han, Xiaoqiang, He, Lin, Dai, Bin

Sulfoximines derivatives are widely used in the field of pesticides and medicine due to its antimalarial, antibacterial, and herbicidal properties. A concise and direct synthetic strategy for the construction of trifluoromethylated cyclicsulfoximines have been developed via [3+2] cycloaddition reaction of benzynes and trifluoromethylα,β-unsaturated N-(S)-tert-butyl sulfinylketoimines. The reaction affords the cyclosulfoximines at room temperature in low to moderate yields（13%-57%） and KF as fluorinated reagent, 18-C-6 as additives, and acetonitrile and toluene as mixed solvent (V/V=4/1). The insecticidal activities against Aphis gossypii was determined by impregnation method and the results showed that 24-h median lethal concentration （24h LC₅₀）of compound 3b is lower than the positive control imidacolprid (0.0800mg/L) and dinitraz (0.0532mg/L). They can be used as new lead insecticidal compounds with further structure modification

Research Progress in the Cyclization Reactions with Propargyl Alcohols

Propargyl alcohols as a classical bifunctional group compounds possess alcohol hydroxyl group and carbon-carbon triple bond. Due to their special structure, they show unique reaction characteristics, and are employed in reactions via activating its alcoholic hydroxyl group or the triple bond. The most typical reaction for propargyl alcohols is various cyclization reactions with different compounds to assemble a richer variety of cyclized compounds, such as: cyclopentene, pyrrole, furan, cyclic carbonate, pyran, pyridine and azepine cyclic compounds. This review aimed to summarize the recent research progress in the cyclization reaction of propargyl alcohols with various compounds, including [3+2], [2+3], [3+3], [4+2], [2+4], [4+1], [3+4] and other types of cyclization reactions.

Study on the Secondary Metabolites of the Endophytic Fungus Aspergillus terreus HQ100X-1 in Scutellaria formosana

Two new compounds (1~2) together with ten known compounds were isolated from Scutellaria formosana endophytic fungus Aspergillus terreus HQ100X-1, terrustone (1) is a trihydroxycyclopentanone with four consecutive chiral centers. Their structures were determined by 1D/2D NMR data along with ECD calculation for configurational assignment. Compound 4 showed antibacterial activity against Staphylococcus aureus with MIC value of 2.5 μg/mL.

Recent Progress in Transition Metal-Catalyzed C-H Bond Activation of N-Aryl Phthalazinones

Gu Haichun, Jin Xinxin, Li Jiaqi, Li He, Liu Jinglin

N-aryl phthalazinones are important nitrogen heterocycles widely existing in the natural products, and drug molecules. Meanwhile, N-aryl phthalazinones are also very significant substrates for organic synthesis. In recent years, with the development of C-H bond activation catalyzed by transition metal, the synthesis of nitrogen heterocycles via the C-H bond cleavage of phthalazines derivatives has attracted attention of chemists. In this paper, the recent progress of the transition metal-catalyzed C-H bond activation reaction of phthalazines is reviewed by classifying different coupling components, and the reaction mechanism is discussed.

A Feasible Route to Access the ABD Skeleton in Azadirachtin-type Limonoids

Dong Chang-ming, Xie Yi, Liang Guang-xin

In an effort to rapidly construct the azadirachtin-type limonoids and analogues, a highly diastereoselective synthesis of the ABD tricyclic core in azadirachtin-type limonoids from (-)-carvone has been developed. The synthetic avenue features an INOC reaction to assemble the trans-decalin system in highly stereoselective manner. By further utilizing an efficient sequence of Sonogashira coupling, isoxazoline reduction, stereocontrolled dihydroxylation, mesylation and intramolecular S_N2 substitution, we achieved a scalable stereoselective synthesis of the tricyclic core skeleton of azadirachtin in 13 linear steps with with 6.1% total yield. This intermediate can serve as a highly functionalized left-wing fragment for the synthesis of azadirachtin and its analogus. Compared with existing methods, the methods reported herein are simple, reliable, easy to implement, and significantly advances research on the synthesis of the azadirachtin-type limonoids.

Application of the Radical Polyene Cyclization Reaction in Natural Product Synthesis

Liangcai Yao, Jinghan Gui

Polycyclic compounds, which exist widely in natural products, synthetic drugs, agrochemicals, fine chemicals, etc. have a wide range of biological activities. Therefore, efficient synthesis of polycyclic compounds is an important research direction in organic synthesis. In recent years, free radical cascade cyclization of polyenes has increasingly become a reliable and concise way to construct polycyclic skeletons. However, the research papers on free radical cascade cyclization, especially those initiated by the homolysis of epoxides, have not been summarized. Therefore, this paper mainly reviews the initiation methods of free radical polyene cascade cyclization and its application in the synthesis of polycyclic natural products, with an emphasis on the Ti(III)-mediated free radical cascade cyclization of polyene epoxides.

Fermentation Optimization of the Caerulomycin H-producing strain CRM05 and the Systhesis of Cyanogriside K

Yun Luo, Yukang Gao, Pengcheng Yan, Weiming Zhu

Caerulomycin H and its 4-yl α-L-rhamnopyranoside (cyanogriside K) are two microbial natural products from marine-derived Actinoalloteichus cyanogriseus WH1-2216-6. Cyanogriside K (1) showed good antiproliferative activity against tumor cells, whereas the yield is very low and the synthesis have not been reported. Thus, our first goal is to obtain enough caerulomycin H by optimazing the fermentation condition of the mutant strain CRM05 of A. cyanogriseus WH1-2216-6. The yield of caerulomycin H reached 272 mg/L, a 5-fold increase than the original production, in the optimal solid medium consisted of corn pellets (80 g) and liqiud medium 5# for actinomycetes (100 mL). Then cyanogriside K was synthesized with 25.6% total yield from caerulomycin H by six steps' reactions including deoximation, rhamnosylation, oximation and deacetylation. The structure of cyanogriside K (1) was identified by NMR, HRESIMS and specific rotation as the same to the reported natural product. Furthermore, cyanogriside K showed good bioactivity against the proliferation of the tumor cell lines, PATU8988T, 786-O, 5673, DU145, A-375, FaDu and SF126, with IC₅₀ values ranging from 1.07 μM to 1.78 μmol/L.

Tris(4-ethynylphenyl)amine-based Conjugated Microporous Polymers and its Photocatalytic Water splitting Hydrogen Evolution

Conjugated microporous polymers (CMPs) have shown attractive application prospects in the field of photocatalytic water splitting hydrogen evolution since their excellent stability and adjustable properties. To develop novel multi-functional building blocks for CMPs photocatalysts and explore effective methods to tune their properties, based on tris (4-ethynylphenyl) amine (TEA) unit and benzothiadiazole (BT) unit with different linking positions, four CMPs FS1, FS2, FS3 and FS4 have been synthesized with Sonogashira-Hagihara coupling reaction. The linking position of BT units in them are 5,6 -, 4,5 -, 4,6 - and 4,7 - respectively. It suggests that the four polymers all have stable photocatalytic hydrogen evolution performance under visible light driving. FS4 with 4,7-linked polymer has the best performance, and its hydrogen evolution efficiency is as high as 115.74*10^-3 μmol mg^-1 h^-1, nearly three times than that of FS1. It shows that TEA is an excellent multi-functional building block of CMPs photocatalyst, and the linking position of BT unit regulation is an effective means to tune the performance of TEA based CMPs.

The SCF₃ Radical Initiated Cascade Reaction of Unsaturated Hydrocarbon

Shi Yun, Xiao Ting, Xia Dong, Yang Wenchao

Fluorinated compounds have been widely used in pharmaceuticals, pesticides, and other disciplines due to their special physical and chemical properties, which motivates the frequent introduction of fluorinated functionalities into lead compounds to improve their physical and chemical properties. The trifluoromethylthio (SCF₃) group with high electronegativity and special lipophilicity plays an important role in a multitude of fluorinated compounds. This review summarizes recent progress in the field of cascade reaction of unsaturated hydrocarbon initiated by SCF₃ radical, including reaction design, reaction mechanism, and outlook.

A Lysosome-Targeted Far-Red to Near-Infrared Fluorescent Probe for Monitoring Viscosity Change During The Ferroptosis Process

Elucidating the intrinsic complex relationship between pathophysiological processes and lysosomal viscosity is a tremendous challenge. So far, the change of lysosomal viscosity during the ferroptosis process has not been reported. In this study, we designed and synthesized a novel far-red to near-infrared viscosity fluorescent probe(FNVP) based on BODIPY dye. The probe exhibited excellent responsiveness to viscosity change (λ_ex = 600 nm, λ_em = 680 nm). In the PBS-glycerol system(1~219 cP), the emission intensity of probe FNVP at 680 nm had about a 50-times increase. Furthermore, the probe showed the advantages of high selectivity, remarkable photostability and negligible cytotoxicity. Probe FNVP was lysosome-targetable and could be used for monitoring lysosomal viscosity changes induced by nystatin. Finally, using confocal fluorescence microscopy, we imaged lysosome viscosity during the ferroptosis process at the cellular level. All those will be beneficial to further comprehending the biological effectiveness of ferroptosis.

Transition metal-free selective aerobic C-alkylation of methyl N-heteroarenes with alcohols

Tianyu Chen, Feng Han, Shuangyan Li, Jianping Liu, Jianhui Chen, Qing Xu

By performing the reaction under air using a suitable base, selective C-alkylation of methyl N-heteroarenes with various alcohols can be effectively achieved without using any external catalyst. Control experiments reveal that transition metal catalysts are indeed not needed in the reaction. Mechanistic studies reveal that base and air can play crucial roles, so that the reaction is in effect initiated by base-promoted aerobic oxidation of the alcohols to carbonyl intermediates, which can then catalyze the C-alkylation reaction to selectively afford the alkylated N-heteroarenes and be regenerated and recovered to furnish the catalytic cycle. This method has obvious advantages of broad substrate scope, requiring no transition metal catalysts/ligands and inert conditions, simple operation, low cost, no transition metal residue contaminant in the products, and is thus a practical way for functionalization of the N-heteroarene compounds.

Nickel-Catalyzed Heck Reaction of Cycloalkenes with Inert C-O Bonds of Aryl Carbonates and Aryl Sulfamates

Zeng Xuqun, Zhang Qian, Wu Xufeng, Zhang Jingfeng, Zhang Xinwei, Huang Xiaolei

An efficient nickel-catalyzed Heck reaction of cycloalkenes with inert C-O bonds of aryl carbonates and sulfamates has been developed. Both naphthyl, heterocycles and simple phenyl substituted carbonates with various functional groups are compatible with the catalytic systems comprising Ni(II), PhBPE ligand and reductive metal Zn.

Cytotoxic Polyketides from the Deep-Sea-Derived Fungus Talaromyces indigoticus FS688

The chemical investigation of the deep-sea-derived fungus Talaromyces indigoticus FS688 led to the isolation of three new polyketides (1~3) together with five known compounds (4~8). The structures were determined by comprehensive spectroscopic analysis and the absolute configuration were evaluated by theoretical ECD calculations. Comound 2 exhibited significant cytotoxicity against the four tested human tumor cell lines SF-268, MCF-7, HepG-2 and A549 with the IC₅₀ values in the range of 0.18~0.53 µM.

Design, Synthesis and Bioactivity evaluation of Guaiazulene Derivatives with Antioxidant and Anti-inflammatory Activities

Li Lei, Zhu Congcong, Zhu Quangang, Chen Zhongjian, Gao Xike

Animal and plant-derived guaiazulene (GA) has the characteristics of antimicrobial, antioxidant, anti-inflammatory, anti-allergic and low toxicity. Sodium guaiazulene sulfonate (GAS-Na), a water-soluble derivative of GA, also has the effects of anti-inflammatory, promoting epithelial cell growth and wound healing. However, the commercial active molecules GA and GAS-Na has poor stability to light and heat. Therefore, in order to explore the guaiazulene biomedical functional molecules with higher activity and stability, 2,2'-biguaiazulene (BGA) and [2,2'-biguaiazulene]-1,1'-disulfonic acid sodium (BGAS-Na) were synthesized. Compared with GA and GAS-Na, the antioxidant activities of BGA and BGAS-Na were evaluated, and their biological effects on NO release and cell viability of LPS-induced RAW 264.7 macrophages were studied. The results showed that BGA and BGAS-Na had better antioxidant capacity and improved stability compared with GA and GAS-Na; BGAS-Na had the best NO inhibition rate in the anti-inflammatory activity test (the IC₅₀ value was 5.64 μg/ mL), which was better than that of the commercial molecule GAS-Na, and the inhibitory effect was dose-dependent. In addition, the four compounds did not affect the growth of macrophages and had low cytotoxicity. Therefore, BGAS-Na is expected to become a potential anti-inflammatory drug.

Base-Catalyzed Selective Hydrogen-Deuterium Exchange in Mono-1-Substituted 1,2,3-Triazoles

An effective and selective deuteration of mono-1-substituted 1,2,3-triazoles using base-catalyzed hydrogen-deuterium exchange is proposed. The H/D exchange was selectively conducted at C5 position of 1,2,3-triazoles with catalytic amount of t-BuOK, t-BuONa or Cs₂CO₃ in DMSO-d₆. From corresponding 1,2,3-triazoles via H/D exchange process, 5-deutero and 4-deutero mono-1-substituted 1,2,3-triazoles were respectively given from corresponding 1,2,3-triazoles. In addition, the triazole-induced deuteration on phenyl ring was observed.

Research Progress of DDR1 Inhibitors

Ge Tianpeng, Yang Yanchen, Li Chunpu, Zhang Jian, Liu Hong

Discoid domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase that plays a key role in regulating important processes, such as cell differentiation, proliferation, adhesion, migration, invasion and matrix remodeling. Overexpression or activation of DDR1 is closely related to the occurrence and development of inflammation, as well as tumor invasion and metastasis. Therefore, DDR1 is a potential target for the treatment of diseases, such as inflammation, fibrosis and malignancy. Since the early 1990s, a variety of DDR1 small molecule inhibitors have been reported successively. This article focuses on the structure, function, mechanism and signaling pathways of DDR1, and reviews the design, structure-activity relationship and pharmacological activity of DDR1 small molecule inhibitors from the perspective of medicinal chemistry.

Synthesis and Antitumor Activity of Hederagenin Derivatives

Using hederagenin as lead compound, three series of novel hederagenin derivatives A1-A5, B1-B8 and C1-C2 containing various heterocycles were designed and synthesized. Its structure was characterized by ¹H-NMR, ¹³C-NMR and HRMS. The performance of these compounds on human non-small cell lung cancer cells (A549), human breast cancer cells (MCF-7), human colon cancer cells (HCT116), human colon cancer cells (SW620), human hepatoma cells (HepG-2) and human hepatoma cells (BEL7402), in vitro antitumor activity was evaluated by thiazolyl blue (MTT) method. The experimental results showed that compound A5 (IC₅₀ = 2.05 μM) had the strongest anti-proliferative activity on HCT116 cells. Western blotting experiments showed that compound A5 may exert its antitumor activity through NF-κB signaling pathway.

Synthesis of Selenylated Spiro[indole-3,3′-quinoline] Derivatives via Visible-Light-Promoted Isocyanide Insertion

Liu Haoyang, Sun Shuangshuang, Ma Xianli, Chen Yanyan, Xu Yanli

A photosensitizer-free visible-light-promoted isocyanide insertion protocol for the synthesis of selenylated spiro[indole-3,3′-quinoline] derivatives has been developed, which has the advantages of functional group tolerance, broad substrate scope, simple operation, and good yield. The products 3g, 4d, and 4g showed potent cancer-cell-growth inhibitory activities by MTT assay.

Research Progress in Synthesis of Indole Alkaloids Vindoline and Vindorosine

Kong Xiangkai, Zhang Yipeng, Dang Lingjing, Chen Wen, Zhang Hongbin

Vindoline and vindorosine are two Aspidosperma-type indole alkaloids isolated from the leaves of Catharanthus roseus. Both compounds have highly functionalized pentacyclic indoline skeleton and six contiguous stereogenic centers, three of which are congested quaternary carbon centers. In view of the complex structures of these two molecules and their great challenges in synthesis, 15 research groups have carried out the synthesis of these two molecules. This article reviews the progress of the synthesis of these two molecules in chronological order.

Research Progress of Sulfoxonium Ylides in the Construction of Five/Six-Membered Nitrogen-Containing Heterocycles

Zhang Jiantao, Zhang Cong, Zheng Zidong, Zhou Peng, Liu Weibing

Sulfoxonium ylides are witnessed as powerful reagents for various organic transformations due to its high stability and diverse reactivity in organic synthesis. This review systematically summarizes the research progress of sulfoxonium ylides involved in the construction of nitrogen-containing heterocyclic compounds. The new methods and progress of sulfoxonium ylides as an important synthon to construct five-membered and six-membered nitrogen-containing heterocyclic compounds, such as pyrrole, imidazole, indole, quinoline, quinoxaline, and cinnoline, are summarized, and the future development trend of green synthesis of nitrogen heterocycles from sulfoxonium ylides is also prospected. We expect that this review will inspire chemists and elucidate the new directions of their innovations in this field.

New Routes to Antiviral Molnupiravir against SARS-CoV-2 Infection

Liu Zheng, Yang Jing, Liu Feng-Wu

Molnupiravir is an oral drug against SARS-CoV-2 infection approved by Britain and America in 2021. Currently, the reported synthetic methods of molnupiravir have disadvantages, such as long steps, limited yield and high cost. Efficient methods for the synthesis of molnupirovir through direct acylation of low-price cytidine are developed herein. In different proportions of aqueous tetrahydrofuran solution, selective isobutyrylation of hydroxyl of cytidine and further 2',3'-deprotection of 2',3',5'-tri-O-isobutyrylcytidine could be realized, which successfully gave 5'-O-isobutyrylcytidine. Finally, N⁴-hydroxylation of 5'-O-isobutyrylcytidine yielded molnupirovir. Using this straightforward and high-yielding three-step approach, molnupirovir was obtained from cytidine in 82% overall yield.

Blue Light Induced Insertion of Carbene into C(CO)-C Bonds of 1,3-Diones

Ba Dan, Cheng Guolin

Visible light is an ideal “tool” for the green chemical synthesis. Visible light-induced reactions show such advantages as mild reaction conditions, simple equipments, and less by-products. Therefore, it has gradually become an important method in organic synthesis. We reported herein an blue light induced LiBr-promoted carbene insertion reaction of diazoesters into C(CO)-C bonds of 1,3-diones for the synthesis of a wide range of all-carbon quaternary center-containing 1,4-dione derivatives. The method features good substrate universality and functional group compatibility, and therefore, is an ideal and efficient strategy for the synthesis of 1,4-diones.

Recent Advances in Chemical Protein Modification via Cysteine

Wang, Changliu, Zhao, Yongli, Zhao, Junfeng

Proteins are the most abundant biomolecules in cells and involved almost all processes of living activity. Chemical modification of proteins is an efficient strategy to mediate and study the physical and chemical properties and biological functionalities of proteins. Most protein chemical modifications are based on the bioorthogonal reactivities of the side chain functional groups of certain amino acid residues. Among 20 proteinogenic amino acids, cysteine has been the most widely used for chemical protein modification, owning to its relative low abundance in proteins, the unique nucleophilicity and low redox potential of its mercaptan group. In this review, we have comprehensively reviewed the recent advances in chemical protein modification via cysteine and discussed the challenges and applications for future development.

Discovery and Structure-Activity Relationship Studies of Thiazole-Oxazole Tadem Heterocyclic RNA Splicing Inhibitors

Zhang, Rong, Gao, Xiang, Chen, Lingling, Nan, Fajun

Precursor mRNAs (pre-mRNAs) undergo splicing to remove introns and ligation of their exons to yield mature mRNAs. Pre-mRNA splicing is an essential component of gene expression and proteomic diversity in higher organisms. However, the alternative splicing or mutation of splicing factors have been found in human diseases. By the use of the small molecules modulate the splicing process, will provide potential treatment for related diseases. In this paper, circmcherry expression system was used to screen compounds that could affect splicing process. several simple derivatives of natural product Leucamide A have been found to have inhibitory effects, and 36 compounds with thiazole-oxazole tadem structural core were designed and synthesized, of which compound 9l shows most potent inhibitory activity on splicing.

Research Progress on Light-Promoted Transition Metal-Catalyzed C-X Bond Coupling Reactions

Song, Geyang, Xue, Dong

The photo-transition metal synergistically catalyzed coupling reaction provide a new research strategy for the development of metal-catalyzed coupling reactions. In this catalytic system, the excited state photosensitizer controls the valence state of the transition metal intermediate through a single electron transfer process, there by regulating the coupling reaction process, especially for the process that is difficult to occur in traditional transition metal catalysis. In addition, excited photosensitizers could also promote the coupling reaction through the energy transfer process. Simultaneously, light-promoted transition metal-catalyzed C-X bond coupling reactions without external photosensitizers have also been rapidly developed. Light and transition metals synergistically catalyzed coupling reactions provide an important tool for the construction of C-heteroatom bonds, showcasing broad application prospects in synthetic chemistry.

Photocatalyzed oxidative cross-coupling reaction to access symmetrical/unsymmetrical thiosulfonates

Jianming Zhao, Jiashun Zhu, Jiabin Shen, Yilan Zhang, Wanmei Li

Photocatalysis has become the forefront of international chemical research due to its green and environmentally friendly characteristics. In this paper, we describe a new protocol to construct S-S (O)₂ bonds using selectfluor as oxidant and eosin Y as photocatalyst under blue light irradiation. This method has the advantages of mild conditions, good compatibility of functional groups, and easily preparation of various symmetric or asymmetric thiosulfonates various from the corresponding mercaptans with good conversion rates. Thus, this protocol provides a very valuable reference for developing a catalytic system with mild conditions, high atomic economy and strong universality to achieve efficient and controllable conversion of sulfur-containing organic compounds.

Trifluoromethyl sulfonic anhydride Mediated Addition of Pyridine with Ynamides

Song Hao-Ru, Sun Jian-Ting, Lv Min, Liu Yi-Wen, Wei Bang-Guo

A convenient approach to pyridine quaternary ammonium salts containing enamine fragment has been developed, which features a trifluoromethyl sulfonic anhydride mediated regioselective addition process of pyridine with ynamides. Using this method, a variety of substituted pyridine quaternary ammonium salts containing enamine fragment 3a-3m were prepared in moderate to excellent yields with high regioselectivities (Z:E up to 20:1).

Research Progress in Synthesis and Application of Thiosulfonates

As an important kind of synthons, thiosulfonates can react with alkynes, alkenes, aldehydes, and halogenated hydrocarbons to synthesize thioethers and sulfones. At the same time, some thiosulfonate compounds have anti-viral and anti-fungal bioactivities. The synthesis of thiosulfonates and their applications in organic synthesis have been under the spotlight. Thus, according to different types of catalysts and new progress in green chemistry, the synthesis progress of thiosulfonates is summarized. On the other hand, according to the types of reactants and reaction types, the application progress of thiosulfonates in organic synthesis is reviewed. In the future, among the researches on the construction of new sulfides with thiosulfonates, various difunctionalization reactions are still promising directions.

Recent Progress on Chan-Lam Coupling Reactions Catalyzed by Copper(II) Complexes

Jia Xuefeng, Tong Xiangjuan

Copper-catalyzed Chan-Lam reaction represents an important and highly efficient method for synthesis of organic molecules containing carbon-heteroatom (C-N, C-O, C-S) bonds, which has many advantages such as mild conditions, wide substrates range and high yields. Therefore the Chan-Lam coupling reactions are extensively applied in organic synthesis, medicinal chemistry and material science etc. Although many catalytic systems using different copper salt alone or in combination with various ligands for Chan-Lam coupling reaction have been extensively reported by different groups,the studies on the Chan-Lam coupling reaction employing well-defined copper complexes as catalysts were underdeveloped. In recent years, the Chan-Lam reactions catalyzed by copper complexes with different ligands have attracted more special attention from synthetic chemist and made many achievements. Some copper complexes with novel structure of the ligands have been designed and synthesized, which were further used as efficient catalysts for Chan-Lam coupling reactions of arylboronic acids with various nucleophiles. In this review, the recent progress on Chan-Lam coupling reactions catalyzed by well-defined copper(II) complexes are summarized via homogeneous and heterogeneous catalysis in detail. Then the homogeneous Chan-Lam reactions are classified by the different coordination mode of copper complexes, and the heterogeneous Chan-Lam reactions are described according to chronological order. The reaction mechanism on Chan-Lam coupling proposed by different research groups is also straightened out and discussed. Finally, the development prospects of this research field are pointed out.

Synthesis and Fungicidal Activity of Novel Butenolide Compounds Containing Oxime Ether Moiety

Zhang Qian, Li Yihao, Xu Leichuan, Ma Haoyun, Li Xiangdong, Wang Mingan

A series of novel butenolide compounds containing oxime ether moiety were designed and synthesized through diversity modification of the benzene ring at 4-phenyl and the 3-oxime ether group based on the fungicidal 3-acetyl-4-phenyl-1-oxaspiro[4,5]dec-3-en-2-one oxime ether as the lead structure, their structures were characterized by ¹H, ¹³C NMR, HR-ESI-MS data and X-ray diffraction. The preliminary in vitro bioassay results indicated that some of these compounds exhibited good fungicidal activities against Thanatephorus cucumeris, Sclerotinia sclerotiorum and Botrytis cinerea. For example, (E)-3-(1-((2-chlorobenzyloxy)imino)ethyl)-4-(pyridin- 2-yl)-1-oxaspiro[4.5]dec-3-en-2-one (A₇) had EC₅₀ values of 6.02, 8.25 and 15.70 mg/L against T. cucumeris, S. sclerotiorum and B. cinerea, (E)-3-(1-((2-chlorobenzyloxy)imino)ethyl)-4-(pyridin-4-yl)-1-oxaspiro[4.5]dec-3-en- 2-one (A₈) had EC₅₀ values of 1.31 and 10.62 mg/L against T. cucumeris and S. sclerotiorum, respectively. A₇ had an excellent inhibition against spore germination of B. cinerea, the inhibition rate was 95% at the concentration of 100 mg/L. The in vivo bioassay results showed that compounds A₇ had a notable protective activity against tomato gray mould and rice sheath blight disease.

Synthesis of Quinazolin-4(3H)-ones via Ammonium Iodide-Catalyzed Dual Amination of sp³C-H Bonds

Yu Xiaoxiao, Bai Wangheng, Zhu Jianye, Zhang Yuting, Zhang Mengru, Wu Jiwei

A novel method for synthesizing quinazoline-4(3H)-ones was developed by using inexpensive ammonium iodide as catalyst via dual amination of aromatic benzylic position sp³C-H bonds. In this reaction, ammonium iodide was used as catalyst, tert-butanol hydrogen peroxide (TBHP) was used as oxidant and dimethyl sulfoxide (DMSO) was used as solvent. The reaction was carried out at 100 ℃ for 20 h to obtain quinazoline-4(3H)-ones compounds with moderate to excellent yields. Furthermore, the mechanism investigations were conducted, and the possible reaction mechanism was depicted. Due to the method does not require use metal catalyst, and has the advantages of simple conditions and wide substrate application range, the present protocol has the potential to be widely applied.

Construction and Cell Imaging Study of a Novel Fluorescent Probe for ONOO^- Detection

Li Jiaxin, He Ruyan, Duan Senlin, Li Jinhua, Han Xiaojing, Ye Yong

As an important reactive nitrogen species, peroxynitrite (ONOO^-) is closely related to the occurrence of various diseases. The development of methods to detect ONOO^- is of great significance for understanding its related physiological and pathological mechanisms. In this paper, a novel ONOO^- fluorescent probe TPE-ONOO was successfully constructed based on tetraphenylethylene as a fluorophore and a pyrylium group as the specific recognition site of ONOO^-. The probe showed high selectivity, strong anti-interference ability and high sensitivity to ONOO^-. Cell assays suggested that the probe has low cytotoxicity and was successfully used for imaging monitoring of exogenous and endogenous ONOO^- in cells. The novel probe reported here provides an efficient tool for studying ONOO^-physiological processes.

BF₃·Et₂O Promoted Dienone-Phenol Type Rearrangement to Synthesize Phosphepine AIEgens

Guo, Ze, Wu, Di, Wang, Lili, Duan, Zheng

Very recently, phosphepines has emerged as a new luminogen. Further explorations of this new motif in optical materials have been hampered by the lack of general and practical methods for their synthesis and derivation. The rearrangement of dienones promoted by acid or base is widely used in the preparation of phenols. A series of phosphepines were synthesized by BF₃·Et₂O promoted dienone-phenol rearrangement of spiro six-membered phosphacycles. The reaction proceeded smoothy with good substrate tolerance and the UV-Vis absorption and fluorescence emission of the resulting phosphepines were investigated. This study provides a new approach for the construction of π-conjugated seven membered phosphacycles with aggregation-induced emission (AIE) proformace.

Visible Light-Induced 4-Chromanones Synthesis: Radical Cascade Cyclization of α-Oxocarboxylic Acids with o-(Allyloxy)arylaldehydes Promoted by PIDA

Zhou, Xuyu, Zhang,aijun, Zhang, Qingqing, Liu Qingan, Xuan, Jun

An efficient and sustainable visible light-promoted cascade radical cyclization of α-oxocarboxylic acids with o-(allyloxy)arylaldehydes towards the construction of 1,4-diketone containing chromanone derivatives has been developed. The reaction occurred under mild reactions, e.g. room temperature, blue LED irradiation, photoredox catalyst free, and provided the final heterocycles in moderate to good yields.

Recent Process in the In situ Generated Metal Nanocluster Catalysis

Zhang, Jinyu, Liu, Tianfen, Wang, Le, Wang, Xiaoming

In transition metal catalyzed reactions using simple metal salts, metal complexes, or nanoparticles as catalyst precursors, the metal sources may transfer to other species in situ, such as mono metal species, metal clusters and nanoparticles. Herein, representative examples of the in situ generated metal nanoclusters as the catalytically active species in synthetic methodologies are reviewed, including their in situ formation, characterization and effect in catalysis.

Advances on Asymmetric Reductive Amination with Ammonium Salts as Amine Sources

Zengjin Dai, Xumu Zhang, Qin Yin

α-Chiral primary amine subunits are widespread structural units in a large number of pharmaceutical molecules and are key intermediates toward the preparation of numerous amine-containing drugs. Versatile functionalizations on the NH₂ group also supply a quick way to construct molecular complexity. Additionally, chiral primary amines can serve as ligands or organocatalysts which can be applied in organic synthesis. Therefore, efficient synthetic routes toward chiral primary amines have attracted tremendous attention. Asymmetric chemo-catalytic reactions that are capable of directly preparing chiral primary amines remain scarce. Transition-metal-catalyzed asymmetric reductive amination (ARA), a reaction type that transforms easily available ketones and amines into chiral amines in the presence of a chiral metal-catalyst and reductant, is among the most straightforward methods to access chiral amines. However, studies on ARA are still limited compared to that on imine hydrogenation, probably due to the presence of competitive ketone reduction as the side reaction. ARA using ammonium salts as the amine sources can directly yield chiral primary amines from prochiral ketones and are thus highly attractive and of great significance. In addition to competition with ketone reduction process, this reaction also faces some other challenges, including: (1) NH₃ or the produced primary amines can coordinate to the metal center which results in catalyst poisoning effect; (2) the coordination of amine ligand to the metal center may lead to ligand exchange that enhances the challenge on asymmetric control; (3) the produced primary amines may undergo further alkylation process via double reductive amination, thus providing more complicated outcome. The existing problems and challenges in ARA require urgent development of applicable catalytic systems. Aiming to solve some challenges in the field of ARA with ammonium salts, we have carried out systematic studies and will present the latest progress achieved from our team in this account.

Research progress of Chan-Lam coupling reaction in heterogeneous catalysis

Rui Bai, Xu-Juan Liu, Wen-Yu Luo, Shanshan Liu, Lin-Yu Jiao

As a classical method of C—N bond formation, the research on Chan-Lam coupling has made great progress recently. The reaction system is more mild and green, especially the related research on heterogeneous catalytic system, which lays a foundation for the performance improvement, recovery and reuse of the catalyst. Starting from the design, synthesis and performance research of catalyst supporters and organic ligands, it summarizes the application of supported and coordinated heterogeneous catalysts in Chan-Lam coupling reaction in recent years.

Advances in Catalytic Asymmetric Reactions Using 2-Indolylmethanols as Platform Molecules

Zhang, Hong-Hao, Shi, Feng

Indole-based chiral heterocycles constitute a class of important heterocyclic compounds that are found in numerous natural products, pharmaceuticals, pesticide, and functional materials. The efficient and highly enantioselective synthesis of chiral indole derivatives has become one of the most important issues in organic chemistry. Due to the simple reactivity of the traditional indoles, their involved catalytic asymmetric reactions are very limited, resulting in the limited types of constructed indole-based frameworks. To solve these challenging issues, chemists devised a strategy of introducing simple functional groups to the indole ring, thus obtaining a series of functionalized indole derivatives, namely indole-based platform molecules, as efficient building blocks for constructing chiral indole-related frameworks. Among them, 2-indolylmethanols are a class of important platform molecules, which were designed on the consideration that the introduction of a hydroxymethyl group to C2-position of the indole ring would change the reactivity and the reactive site of the indole ring. This class of platform molecules can either act as electrophiles or nucleophiles, and can act as multi-carbon building blocks in catalytic asymmetric reactions. Therefore, the design and development of 2-indolylmethanols as platform molecules have provided a new strategy for the efficient and highly enantioselective synthesis of chiral indole derivatives. This review summarized the advances in catalytic asymmetric reactions using 2-indolylmethanols as platform molecules, which will open a new window for designing and application of new types of indole-based platform molecules.

Research Progress of Reactions Participated by α-Hydroxy Ketones

α-Hydroxyl ketones are an important class of compounds. They are not only the key structural fragments of many biologically active natural products, but also the important synthetic building blocks, hence α-hydroxyl ketones are employed in the synthesis of various biologically active molecules and drugs. Since the nucleophilic addition reactions and the cycloaddition reactions involving α-hydroxyl ketones have not been reviewed so far, we will sort out and summarize these reactions in this review.

One-pot synthesis of N-isoindolinones via reductive amination/lactamization of methyl 2-formylbenzoate

Zhang, Wensheng, Li, Yan,cui, Haiyan, Su, Xiaoli, Xu, Supeng

An efficient, one-pot synthesis of N-substituted isoindolinones by an aminative reduction/lactamisation sequence of methyl 2-formylbenzoate is introduced. The reaction process includes aminative reduction of o-phthalaldehydic acid methylesters with primary aryl or alkyl amines using NaBH₃CN and the following intramlecular nucleophilic N-attack on carbonyl carbon atom. For 4-substituted aromatic amines, alkyl amines and o-methylaniline, the transformation can be successfully completed in 1,2-dichloroethane at rt. For other 2-substituted aromatic amines, reflux in acetonitrile for 8 h in the presence of K₂CO₃ (2 eq.) is needed.The reaction scopes were quite broad and up to 96% yield of diverse products was achieved.

Pd(II)-Catalyzed Enantioselective C-H Olefination of 2-(Arylsulfinyl)pyridines through Kinetic Resolution

Ling-Jie Fan, Tao Zhou, Xu Yang, Meng-Xue Jiang, Xinquan Hu,bing-Feng Shi

A Pd(II)-catalyzed enantioselective C-H olefination of 2-(arylsulfinyl)pyridines through kinetic resolution is developed. A wide range of chiral sulfoxides were prepared in good to high yields and selectivity (up to 99% ee, s-factor of up to 200) under mild conditions using cheap and commercially available L-pGlu-OH as chiral ligand. This protocol is easy to scale-up and compatible with various acrylates bearing core structures of natural products and scale-up reaction.

Visible-Light-Induced Denitrification Oxygenation Reaction of α-Diazoesters to Construct α-Oxyimido Esters

Visible-light-induced denitrification oxygenation reaction of α-diazoesters with N-hydroxyimides to access α-oxyimido esters has been developed. This reaction provides an efficient approach to synthesize a series of N-hydroxyimides at room temperature in 1,4-dioxane under irradiation of 3 W blue LED lamps without any photocatalyst. Interestingly, when tetrahydrofuran (THF) was used as the solvent, structurally diverse α-oxyimido esters could be rapidly and efficiently obtained through a three-component coupling reaction of α-diazoesters, THF, and N-hydroxyimides. The reaction could conduct on a gram scale without a significant loss of reaction efficiency, indicating that this method could serve as a practical protocol to synthesize α-oxyimido esters.

CNN-Type Binuclear Cu(I) Complexes Catalyzed C-H Bonds Carboxylation via the Fixation of CO₂ at Ambient Conditions

Fei Chen, Sheng Tao, Ning Liu,bin Dai

A type of CNN-type binuclear Cu(Ⅰ) complexes are used in the direct carboxylation of the terminal alkynes under room temperature and atmospheric CO₂ with a low catalyst loading. A broad range of the terminal alkynes were tolerated, leading to the desired propiolic acids in 83%-97% yields. The method was successfully applied to continuous carboxylation and esterification of hetero arenes. The control experimental results and literature suggest that Cs₂CO₃ promotes the removal of terminal alkyne hydrogen atoms, and Cu(Ⅰ) complexes play an important role in the activation of terminal alkyne by the interaction between Cu(I) center and alkynyl group.

Direct Synthesis of 3-Sulfonylquinolines from N-Propargylanilines with Sulfonyl Chlorides

Ke-Li Wang, Jing Huang, Wei Liu, Zhi-Lin Wu, Xian-Yong Yu, Jun Jiang, Wei-Min He

3-Sulfonylquinolines broadly exist in plenty of bioactive molecules and synthetic pharmaceuticals. Herein, we report an efficient and facile method for direct synthesizing various 3-sulfonylquinolines through one-pot sequential hydraznation/sulfonylation/cyclization reaction from N-propargylanilines and sulfonyl chlorides under mild reaction conditions. This procedure not only can be performed on a gram scale but also be applicable to prepare marketed pharmaceutical derivative.

Nickel-Catalyzed Stereoselective Aryl-Difluoroalkylation of Alkynes

Sun Qi, Sun Zeying, Yu Ze, Wang Guangwei

Herein, a nickel-catalyzed aryl-difluoroalkylation of alkynes is developed. A series of trisubstituted fluoroalkenes can be obtained in a highly stereoselective manner by mixing of simple starting materials, alkynes, ethyl bromodifluoroacetate, and arylboronic acids in the presence of nickel catalyst. This method features low-cost catalyst, mild reaction conditions, and excellent functional group compatibility.

NHC-Catalyzed Desymmetrization of Biaryldialdehydes to Construct Axially Chiral Aldehydes

Zhao Wei, Liu Jing, He Xiangkui, Jiang Hao, Lu Liangqiu, Xiao Wenjing

Axially chiral biaryl scaffolds are widely present in natural products, drug molecules, and chiral catalysts and ligands. Therefore, catalytic asymmetric synthesis of chiral biaryls has become an important research topic in organic synthesis. Among them, axially chiral aldehydes are often used as chiral organocatalysts or precursors of chiral ligands in catalytic asymmetric synthesis owing to their unique structural characteristics. For this reason, the development of efficient methods for their enantioselective synthesis has attracted great attention. However, only few catalytic methods have been developed for the construction of structurally diverse axially chiral aldehydes. Herein, we developed a N-heterocyclic carbene (NHC)-catalyzed oxidative esterification reaction to synthesize axially chiral aldehydes through desymmetrization strategy. The This method features mild conditions (room temperature), excellent yields and enantioselectivity, broad substrate scope and good function group tolerance (26 examples, 54-97% yields, up to 99% ee). All the axially chiral aldehyde products have been fully characterized and the absolute configuration was established by comparing the results from known literature. This strategy provides new possibilities for the synthesis of axially chiral aldehydes and their derivatives.

Synthesis of azedarachol、2α,3α,20R-trihydroxypregnane-16β-methacrylate

Gao Ran, Tian Weisheng

Azedarachol (3) and 2α,3α,20R-trihydroxypregnane-16β-methacrylate (4) were isolated from the the root bark of Melia azedarach L. in 1984 by Nakatani and coworkers. Azedarachol (3) shows excellent antifeedant activity against the larvae of Ajrotis sejetum Denis at the concentration of 500 ppm, and 2α,3α,20R-trihydroxypregnane-16β-methacrylate (4) inhibits the HGC27 tumor cells with an IC₅₀ value of (11.3±0.5) ug/mL. The noteworthy activities and the high oxidation state structure as well as the scarce of sample suppling in nature resources have attracted considerable attention from the synthetic community. Herein we report the synthesis of these two natural products from preganetriol (2). The route features a stereoselective inversion at C20 and a substrate controlled dihydroxylation of C2(3) double bond. 3、4 were obtained in an overall yields of 6% (11 steps) and 7.5% (11 steps) respectively.

Design, Synthesis and Application of Trisubstituted Olefinic AIE Molecules

The discovery of aggregation-induced emission (AIE) has created a new milestone and new situation in the research of organic luminescence materials. The research on AIE molecules has attracted enormous attention. Among them, trisubstituted olefinic AIE molecules, as new structural types in recent years, have made remarkable progress in their design, synthesis and application. In view of this, according to the structural characteristics of the substituents attached to the carbon-carbon double bond, these trisubstituted olefinic AIE molecules synthesized in recent years are divided into three categories, (a) olefinic AIE molecules substituted by multiple aryl rings, (b) by cyano group(s) and (c) by heteroatoms. As this classification, their molecular mechanisms and applications in the field of organic luminescence materials and fluorescent probes are reviewed, and the future design of the trisubstituted AIE molecules is also prospected.

A Sulfonamide-substituted Benzothiadiazole-based Fluorescent Dye for Long-term Cancer Cell Tracking

Xia Weikang, Liu Chuanga, Ye Shenga, Wang Lei, Liu Ruiyuan

To develop long-term cancer cell tracking dyes with anti-photobleaching, large Stokes shift, and excellent biocompatibility is the research hotspot in the field of biological imaging. In this study, we sythesized a donor-acceptor-donor (D-A-D) stuctured benzothiadiazole (BTD)-based fluorescent dye, namely SIBIS. The BTD with excellent optical properties was chosen as the core stucture and the N,N-dimethyl substituted sulfonamide was selceted to improve the biocompatibility and solubility of fluorescent dye. SIBIS possessed aggregation-induced emission (AIE), large Stokes shift (155 nm) and low cytotoxicity. The endocytosis results in different cell lines showed that SIBIS could target lysosome of living cells. The long-term 4T1 cell tracking results showed that SIBIS could effectively trace cell divisions for more than 15 generations. Therefore, SIBIS can serve as a kind of promising long-term cell traking agents tumor cells, and has a great potential for further biological applications for tracking various kinds of lysosomal related inflammation and diseases.

NIS Promoted Synthesis of 3-Substituted Indole Derivatives

Cunwei Qian, Rong Han, Zhixing Shen, Qian Li, Xuanrong Chen

In this study, using N-halosuccinimide as catalyst, the Michael reaction of indole and its derivatives and α, β- unsaturated ketones can proceed smoothly to synthesize 3-substituted indoles. Firstly, the Michael addition reaction of indole with chalcone was used as the template reaction, and the optimal conditions of the reaction were explored. The experimental results show that the isolated yield of this reaction could reach 90% with 10 mol% NIS as catalyst and CH₃CN as solvent at room temperature for 18 hours. Under this optimized conditions, the reaction of chalcone and its derivatives with various α, β- unsaturated ketone can proceed smoothly to obtain aimed product. The yields of these reactions ranged from 51% to 89%. The reaction conditions are mild and the reaction operation is simple.

Recent Advances in C-X Bond Metathesis Reactions

Yu Bangkui, Huang Hanmin

Metathesis reaction, as a new type of chemical bond reorganization reaction, proved remarkably powerful for constructing inaccessible complex molecules by other methods in both industrial and academic settings, which greatly promotes the development of synthetic chemistry. However, most of the known metathesis reactions are mainly limited to the recombination reaction of multiple bonds, and the metathesis reactions of C-X single bonds are still in their infancy and face many opportunities and challenges. This is mainly due to the high bond energy of the C-X bonds, which is hard to break and reorganize. The progress of C-Si, C-P, C-S, C-I, C-O and C-N bonds metathesis reactions and their applications in organic synthesis are summarized according to the type of bonding.

Structures and Synthetic Strategies of Chiral Oxazolinyl Ferrocene Derivatives

Dai Li, Mao Yifei, Zhu Jiaqi, Yang Mengjiao, Xu Di

In the past two decades, chiral oxazolinyl ferrocenes and their corresponding transition-metal complexes have been investigated as one of the most significant catalysts in asymmetric transformations. Synthesis of oxazolinyl ferrocenes established the key structural foundation for achieving the chiral catalysts with excellent activity and stereoselective control. In this review, we surveyed the typical derivatives with oxazolinyl ferrocenes framework, and overviewed the practical preparation strategies for chiral oxazolinyl ferrocenes in recent years. We here also delivered potential challenges and further applications in the field of oxazolinyl ferrocene derivatives.

Cyclization and Coupling Reactions Promoted by Potassium tert-Butoxide

Zhang, Lizhi, Liao, Yongjian, Chen, Ning, Huang, Lei, Zhou, Min

Over the past few decades, transition metal-catalyzed reactions have been developed into a powerful tool for building various chemical bonds. At the same time, non-metal-promoted chemical bond construction reactions have attracted more and more attention of synthetic chemists because of the avoiding of using nobel metal catalysts and ligands, resulting in the reduce of reaction costs and environmental pollution. It conforms to the concept of green chemistry development. Among them, potassium tert-butoxide-promoted cyclization and coupling reactions have been rapidly developed. This paper summarizes the intramolecular cyclization and intermolecular coupling reactions involving potassium tert-butoxide since 2000, and the possible reaction mechanism are elucidated, which can help chemists better understand the development of this field and promote the development of this field.

Research Progress in Cyanine-based Recognition Probes for G‑Quadruplex DNA

Guan Li, Mao Yongbao, Zhou Yanyan, Feng Xiaowen, Fu Yile

Guanine-rich (G) DNA sequences can form a special nucleic acid secondary structure called G-quadruplex DNA, which is widely distributed in eukaryotic genomes and is closely associated with the formation and development of cancer. The development of small molecule fluorescent probes targeting G-quadruplexes is of great significance for the study of the biological functions of G-quadruplexes in organisms and for targeting anti-cancer drugs. The cyanine dyes are widely used as fluorescent dyes for biolabelling, with the advantages of multiple modification sites and adjustable spectral range. The rigid structural part of the backbone can be bound to the end of the G-quadruplex or groove through π-π stacking, hydrophobic interaction and other non-covalent bonding, inducing different spectral signal changes of cyanine dyes to achieve selective recognition of the G-quadruplex. This has become a hot topic of research in the field of G-quadruplex recognition in recent years. Herein, the research progresses in the field of G‑quadruplex recognition probes based on cyanine dye are reviewed. Molecular design, mechanism and application of this kind of probes are briefly introduced. Moreover, the future trends of Cyanine-based recognition probes for G‑quadruplex are briefly introduced, the review could provide a clue to further design more sensitive and efficient recognition probes for G‑quadruplex detection.

Reaction of Tandem Addition of Aliphatic Amines to Alkenylnitriles Catalyzed by Tris(o-dimethylaminobenzyl)yttrium

Hou, Jin-song, Yang, Gao-sheng

Amidines are nitrogen-containing compounds with very important physiological activities. There are few reports on the synthesis of cyclic amidines catalyzed by rare earth complexes. In this paper, a series of cyclic amidines were synthesized by the tandem reaction of N-H to CN and "C = C" with simple trialkyl rare earth metal complex Y(CH₂C₆H₄NMe₂-o)₃ as precatalyst. The yield was 22% ~ 96%. The method has the characteristics of simple catalyst, mild reaction conditions and 100% atomic utilization. It provides a new way for the construction of cyclic amidines.

Progress in the Synthesis and Derivatization of Norcorrole

Li, Sha, Sun, Ya-han, Meng, Yan-kui, Li, Xiao-fang, Zhang, Shao-wei

In recent years, norcorrole has attracted extensive attention of scientific researchers, owing to its distinct paratropic ring current, high single molecule conductivity, narrow HOMO-LUMO gap, stable redox performance and unique chemical reactivity. The different synthetic methods of norcorrole in recent years are reviewed, with emphasis on the derivatization reactions in four aspects: insertion, substitution, redox and extension of π conjugated system, and the development of norcorrole is prospected.

PhI(OAc)₂-Promoted Dehydrogenation Oxidation for the Synthesis of 2-(Aryl/alkylthio)phenols and 10H-Phenothiazines

A PhI(OAc)₂-promoted reaction for the synthesis of 2-(aryl/alkylthio)phenol derivatives has been developed, which is realized via dehydrogenation oxidation between ortho- C(sp²)-H of phenols and S-H of thiophenols for direct formation of the C-S bonds. Particularly, this method is also successfully applied for the efficient construction of tricyclic 10H-phenothiazines using 2-aminothiophenols as the substrates. All the newly synthesized products are identified by means of ¹H NMR, ¹³C NMR, IR and HRMS. Besides, compound 3i is further confirmed by X-ray single crystal diffraction analysis. The method has the advantages of simple and easily available starting materials, mild reaction conditions, simple operation, as well as high atom economy.

Synthesis of β-Oxopropylcarbamates Catalyzed by ZnO/ Ionic Liquids under Atmospheric CO₂

Xu, Yong, Zhang, Yongxing, Hu, Jia, Chen, Cheng, Yuan, Ye, Francis Verpoort

Carbamate compounds exhibit a broad applicable scope in medicine, pesticide, resin modification, fabric finishing and organic synthesis. We developed a methodology using ZnO/ ionic liquids as the catalyst for the three-component coupling reactions of carbon dioxide (CO₂), secondary amines and propargylic alcohols to produce various β-oxopropylcarbamates. This catalytic system exhibited robust recyclability and broad substrate scope. Moreover, it showed considerable catalytic activity under atmospheric CO₂, indicating its potential in carbon capture and utilization processes.

The Pd-catalyzed Chlorodifluoroethylation Reaction of C-H Bond of Acetanilides with Chlorodifluoroethyl Iodonium Reagents (CDFI)

Chengyao Kimmy Cao, Yaru Niu, Yunchen Jiang, Hongmei Qu, Chao Chen

Difluoroethyl products have a wide range of applications in the fields of biomedicine and materials, and it's important to develop new method to synthesize difluoroethyl compounds. Herein, we disclosed a palladium-catalyzed chlorodifluoroethylation via ortho-C-H activation of acetanilide, using chlorodifluoroethyl(mesityl) hypervalent iodine reagent as the source of -CH₂CF₂Cl. Moreover, adding organic base DBU to the above system, we obtained the difluorovinylated acetanilide products via an elimination reaction.

Synthesis of a Biphenanthrol-Based Confined Phosphoric Acid

Cen Shouyi, Zhang Zhipeng

Chiral phosphoric acids derived from 1,1'-binaphthyl-2,2'-diol (BINOL) and 1,1'-spirobiindane-7,7'-diol (SPINOL) have been widely applied in asymmetric catalysis and displayed excellent enantioselectivities in hundreds of reactions. However, in catalytic asymmetric reactions that involve less sterically hindered nonaromatic substrates, these Brønsted acids usually provide unsatisfactory enantioselectivities due to the relatively loose chiral environment around the catalytically active site induced by the inherent orientational property of the 3,3'-substituents which extend outwardly. In order to develop chiral phosphoric acids that are compatible with these substrates, we designed a 9,9'-biphenanthryl-10,10'-diol (BIFOL)-based confined phosphoric acid by introducing two aromatic substituents which extend inwardly onto the 1,1'-positions of BIFOL. By employing cheap and commercially available m-dibromobenzene as starting material, we first synthesized key intermediate 8-bromophenanthren-9-ol which undergoes oxidative coupling to afford 1,1'-dibromo-9,9'-biphenanthryl-10,10'-diol. After introducing two aryl substituents through Suzuki-Miyaura coupling, the obtained aryl-substituted BIFOL was converted to the targeted molecule by reacting with phosphoryl chloride and hydrolyzing. The structure of the obtained phosphoric acid was confirmed by single crystal X-ray diffraction analysis.

A Novle Quinoline Hydrazone-Based Fluorescent Probe for Sequential Determination of Cu²⁺/Glyphosate and Its Applications

Wu Mianyuan, You Jun, Yu Yanchao, Wu Wenju

A novel quinoline hydrazone-based fluorescent probe L was designed and synthesized useing quinoline-2- carboxylic acid and 7-(diethylamino)coumarin-3-carbaldehyde as raw materials. The spectral properties of probe L was studied by UV-Vis/fluorescence spectrophotometry. The results showed that probe L had obviously ON-OFF fluorescence response to Cu²⁺ in the tetrahydrofuran (THF)/H₂O [V:V=3:7, 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES) 10 mmol/L, pH=7.4] solution, and it displayed efficiency, high specificity and sensitivity. Job's plot and high resolution mass spectrometry showed that the stoichiometry of L-Cu²⁺ complex was estimated to be 1 : 1. Meanwhile, complex L-Cu²⁺ showed high selectivity and good anti-interference ability towards glyphosate through the significant fluorescence enhanced, and the detection limit of complex L-Cu²⁺ to glyphosate could reach 5.6×10^-8 mol/L (9.5×10^-3 mg/L). In addition, complex L-Cu²⁺ was able to sense glyphosate by “naked-eye” according to the change in color yellow from red, and applied to glyphosate detection in the actual water samples.

Synthesis and Nucleotide Recognition Properties of Carborane-Based Benzoimidazolium Cyclophane

Lin Binghan, Zhuo Jibin, Lin Caixia, Gao Yong, Yuan Yaofeng

Two novel carborane-based benzimidazolium fluorescent probes 4a and 4b were synthesized using 1,2-bis(4-benzylbromophenyl)-o-carborane as starting materials. The structure was characterized by IR, ¹H NMR, ¹³C NMR, ¹¹B NMR and ESI-MS, and the recognition properties of probes 4a and 4b for nucleotides were studied by fluorescence and ultraviolet spectroscopy. The results of fluorescence titration showed that probes 4a and 4b could achieve on-off response to uridine monophosphate (UMP), and had good selectivity and sensitivity, the detection limit of probe 4b for UMP could reach 3.41×10^-8 mol/L. The recognition mechanism of the probe 4b was studied by Job's curve and ¹H NMR titration.

Silver-Mediated Trifluoromethylthiolation-Cyclization-Hydrolysis: Access to F₃CS-Containing Quinolinones

Meng Li, Kai Sun

Herein, a practical formal silver-mediated trifluoromethylthiolation cyclization hydrolysis protocol was developed with the cyano group as a radical acceptor. Various structurally diverse F₃CS-substituted quinolinones were obtained in moderate to high yields. Easy scale-up operation and the potential for product derivatization make this method attractive for the preparation of other valuable F₃CS-containing N-heterocycles. Mechanistic studies suggest that the catalytic system involves a radical pathway and H₂O plays an indispensable role in the hydrolysis process.

Synthesis of Nitrogen-Containing Isoindigo derivatives and their applications in Optoelectronic Materials

Luo Licheng, Li Liang, Mu YouBing, Li BoWen, Wan Xiaobo

Isoindigo has played an important role in organic optoelectronic materials as an excellent acceptor building block due to its planarity and electron-withdrawing capability. The modification, of isoindigo has also become the focus of academia. Recently, great achievements have been made in the synthesis of nitrogen-containing isoindigo derivatives and in their applications as optoelectronic materials. The incorporation of nitrogen atom can further adjust the electron push/pull ability and the planarity of isoindigo derivatives, thereby tune their optoelectronic properties. This review summarizes the development of nitrogen-containing isoindigo derivatives, as well as their applications in optoelectronic materials, which we hope would provide useful information for the design of -conjugated optoelectronic materials.

Recent Advances in Transition-Metal-Catalyzed C-H Activation of Pyridone/Isoquinolones

Pyridones/isoquinolones are a kind of important nitrogen-containing heterocyclic compounds, which have good biological activity and unique chemical properties, and play an important role in synthesis chemistry, functional materials, biomedicine and so on. Recently, transition-metal-catalyzed C—H activation has emerged as a more atom- and step-economical strategy for the construction of functionalized pyridones/isoquinolones, and it has attracted the attention of many organic chemists. Herein, the recent advances in transition-metal-catalyzed C-H activation of pyridone/isoquinolone derivatives were summarized according to the types of metal catalysis. An emphasis on the discussion of catalytic system, reaction mechanisms, substrate scopes and synthetic applications is also introduced. Finally, the limitations and development trend of this research field are analyzed and prospected.

Hydrocarboxylation of alkenes with formate salts via photocatalysis

Huang Yan, Zhang Qian, Zhan Lewu, Hou Jing, Li Bindong

A transition-metal-free β-selective hydrocarboxylation of alkenes under mild conditions has been developed using a formate salt as the reductant, carbonyl source. A broad range of alkenes were compatible with this method and can be efficiently converted into value-added carboxylic acid products. This method also features low catalyst loading, good functional group tolerance, easy scalability.

Convenient Cobalt-catalyzed Stereoselective Synthesis of β-D-thioglucosides

Hua, Min, Sun, Yangxing, Zhang, Xueqing, Yao, Hui, Huang, Nianyu

A method of stereoselective synthesis β-D-thioglycosides from the glucosyl-3-pyridinate donor and thiophenols/thiols through the convenient Co(BF₄)₂was reported in this work. The chemical structure of the target compound was confirmed by nuclear magnetic resonance, high-resolution mass spectrometry and single crystal X-ray diffraction. The reaction has good functional group compatibility with all kinds of mercaptans and thiophenols, and can tolerate active sulfur nucleophiles including ester group, phenol / alcohol hydroxyl group, amino group and acetylamino group. It can also be used for the efficient synthesis of thioglycopeptides, which provides a new way for the rapid preparation of thioglycosides.

β-H Regioselective Trifluoromethyl Sulfonylation of Aryl Ethylene

In the presence of cerium ammonium nitrate, the β-H radical sulfonation reaction of aryl ethylene with sodium trifluoromethanesulfinate was reported to give highly regioselective trans-alkene. The advantages of this method were cheap and easy to obtain reaction reagents, mild reaction conditions and simple operation. Moreover, the reaction had a high regioselective and configurational selectivity.

Research Progress of Antiviral Drug Targeting the Main Protease of SARS-CoV-2

Wang, chunxia, Hu, xiaodong, Xu, bin, Cao, chunyang

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 in late 2019 posed a serious threat to the world population. Some effective vaccines are currently approved and widely used, but the long-term efficacy and safety of this intervention is controversial given the highly mutagenic nature of the coronavirus. In addition, some antiviral drugs show better effects, but their safety and universality have not been supported by more data. Coronavirus main protease (3CL^pro) is a special cysteine protease in the coronavirus family, responsible for processing viral polyproteins to produce yield mature non-structural proteins, which play an important role in the life cycle of coronaviruses and are highly conserved, and therefor is considered as a prominent target for antiviral drug. Strucure studies provide valuable insight into the function of this protease and structural basis of rational inhibitor design. This paper reviews the structure of SARS-CoV-2 3CL^pro and the research progress of bright spot inhibitors targeting 3CL^pro so far, and introduces binding mode and the structure-activity relationships of inhibitors and 3CL^pro in detail. Additionally, we broadly examine available antiviral activity, ADMET and animal tests of these inhibitors.

Aminofluorination-based Structural Modification of Curcumol for the Construction of 3D-Shaped Natural Product Fragment Library

Li, Xiang, Zhang, Yifan, Lu, Kailin, Liu, Shihui, Zhang, Yongqiang

The biological significance of sp³-rich synthetic scaffolds with natural product like features yet distinct global frameworks is being increasingly recognized in medicinal chemistry and biochemistry. Herein, a fragment library consisting of 3D-shaped natural product fragments was assembled. Library construction was performed by photocatalytic amidofluorination of Curcumol to incorporate amine and fluorine as potential binding groups and synthetic growth points. Through this strategy we generate a fragment library of 24 fragments, which we demonstrate to have high three-dimensionality, natural product likeness and superior fragment-like properties, covering a novel chemical space in Fragment Based Drug Discovery.

Porous Organic Polymers as Recyclable Heterogeneous Ligand for the Synthesis of Isoindolinone Compounds

It was reported isoindolinone compounds are efficient synthesized with Pd-metalated / porous organophosphorus ligand (Pd / POL-PPh₃) under heterogeneous conditions. Compared with homogeneous conditions, this method has higher yield, at the same time, the POL-PPh₃ can be recycled, which reduces the cost of the reaction. In this reaction, the POL-PPh₃has porous structure without obvious change during the reaction progress of the morphology, this unique stability is the fundamental reason for the high activity and recyclability of POL-PPh₃as heterogeneous ligand.

Design, synthesis and fungicidal activity of novel thiosemicarbazide compounds

In order to find novel candidates for fungicides with high activity, the natural product cinnamaldehyde derivative N-α-amyl -(4-bromophenyl) -propenyl -N'-2', 3' -O-isopropyl -5'-O-uridine formyl hydrazone (A16) was selected as the lead compound , a series of new thiosemicarbazone compounds were designed and synthesized by replacing the ester uridine with thiourea group. The structures of the target compounds were confirmed by ¹HNMR, ¹³C NMR, IR, elemental analysis or HRMS. The bioassay results showed that some compounds had obvious in vitro fungicidal activity at the concentration of 100 μg/mL. Among them, the inhibition rates of compound 2a against B. cinerea, C. orbiculare and A. solani were more than 80%. Compound 2p showed good activity against R. solani, F. graminearum, C. orbiculare and A. solani. Furthermore, compound 2a had better inhibitory activity against B. cinerea (EC₅₀= 1.77 μg / mL) than polyoxin B, and compound 2p had stronger inhibitory activity against R. solani (EC₅₀= 2.07 μg / mL) than Polyoxin B (EC₅₀=15.33μg/mL). Meanwhile, compound 2p showed better chitin synthase inhibition activity (69%) than Nikkomycin Z (52%) at the concentration of 40 μg/mL

Research Progress on C2-C3 Bond Cleavage of Indole and its Derivatives

Huang, Zexin, Yin, Yuqiang, Jia, Fengcheng, Wu Anxin

Indole building blocks widely exist in many important natural products and drug molecules, and are known as star molecules in bioactive drugs. In view of the outstanding value of indole-based molecules in the field of clinical treatment and drug development, the efficient construction, synthetic transformation and late-stage modification of indole molecules has been an enduring research hotspot in the field of organic synthesis. In recent years, the C2-C3 bond cleavage and reconstruction of indoles have played an important role in the construction of complex molecules and the synthesis of drug molecules, attracting extensive research interests from chemists. This paper systematically summarizes the research progress of C2-C3 bond cleavage/reconstruction reactions of indole and its derivatives in recent years with particular emphasis on reaction strategies, substrate scope and mechanisms.

Rhodium-catalyzed Decarbonylative Suzuki-Miyaura Cross-coupling via in-Situ Generation of Acyl Fluorides from Carboxylic Acids

Liu, Xiaojie, Xu, Biping, Su, Weiping

The biaryl frameworks are momentous organic backbones that are commonly occurred in pharmaceutical, functional materials and natural products. By virtue of the distinctive reactivity through state-of-the-art process, decarbonylative couplings, which have bypassed the restriction to specifically substituted (hetero)aryl carboxylic acids of decarboxylative couplings, gradually become unneglected methods in the conversion of carboxylic acid derivatives. Herein, a rhodium-catalyzed decarbonylative Suzuki-Miyaura cross-coupling via in-situ generation strategy of acyl fluorides from carboxylic acids was developed. This protocol shows eminent functional group tolerance with arrays of combinations between carboxylic acid and boronic acid. Furthermore, the reaction offers a new access to those conventionally unattainable biaryl motifs, including natural product and modified drugs.

Recent Advances in Controllable Organic Reactions Induced by Visible Light without External Photocatalyst

Near-ultraviolet and visible light-induced organic synthesis without photosensitizer has attracted much attention for the organic chemists. Since no photosensitizer is needed in the reaction, it makes the reaction system more simple and feasible, and indicates the future development direction for visible-light-induced organic transformations. Visible-light-promoted organic synthesis without photosensitizer is reviewed in this paper. It covers organic photosyntheses in which the substrate/product as a light-absorbing substance, the electron donor receptor (EDA) complex as a light-absorbing substance, and the homolysis of weak covalent chemical bonds under the visible-light irradiation conditions. Moreover, other organic photosynthetic reactions without external photocatalyst are also discussed.

Recent Advances in Lossen rearrangement

Cui, Yin, Zhang, Guofu, Ding, Chengrong

Isocyanate is an important intermediate in organic synthesis, which could be prepared via the reaction of Hoffman rearrangement, Curtis rearrangement or Lossen rearrangement. Considering avoiding the hazardous and potentially explosive reagents, chemists have focused on Lossen rearrangement and made the progress and applications of this reaction. This review aims to systematically summarize the development and applications of the typical reactions of Lossen rearrangement based on its mechanism. The direction of future research is also prospected.

Recent Advances in Geminal-Group-Directed Alkenyl C-H Functionalization

Yazhou Wang, Yuhang Zhu, Lixia Xu, Rui He, Jian Zhang

Vicinal group-directed alkenyl C-H functionalization provides general method toward the synthesis of multi-substituted alkenes, proceeding by the weakly coordination-group (such as hydroxyl, amide, carboxylic acid, amino group etc.) assisted endo-cyclometallation, leading to vicinal C-H functionalization with excellent E/Z selectivities, including alkenylation, alkylation, arylation, alkynylation, allylation, domino cyclization etc. In stark contrast, geminal group-directed alkenyl C-H functionalization attracted much less attentions presumably due to the difficult formation of exo-metallocyles, which greatly inhibited the development of directed alkenyl C-H functionalization. In recent years, several groups have demonstrated the importance of geminal group-directed alkenyl C-H functionalization, including alkenylation, arylation, alkynylation, allylation and iodination. This review introduces the research progress according to the types of geminal C-H functionalization and discusses the reaction mechanisms and applications of specific reactions. The development prospects with outlook are also summarized.

Research Progress on the Asymmetric Cyclization Synthesis of Seven-membered Rings via Transition Metal Catalysis

Mao, Yuanhao, Gao, Yanfeng, Miao, Zhiwei

Seven-membered ring skeletons widely exist in many natural products and drug molecules, and it is of great significance to develop efficient asymmetric synthesis methods for seven-membered ring compounds. This paper reviews the progress in the asymmetric synthesis of seven-membered ring compounds by transition metal-catalyzed cycloaddition reactions since 2000. The future development direction of this field is also prospected.

Lewis Acid Promoted Intramolecular Nucleophilic Heterocyclization of Unsaturated Amides to Synthesis of 2-Oxazolines and Their Applications in Imaging of Living Cells

Xuerong Chen, Liang Qi, Jinpei Huang, Weiwei Zhu, Yifeng Zhou

2-oxazolines and their derivatives are important scaffolds present in the fields of organic synthesis, material science and biomedicine. Here we report an efficient, mild, and metal-free process to synthesis of 2-oxazoline derivatives. Various 2-oxazoline derivatives were synthesized through the lewis acid-mediated intramolecularly nucleophilic heterocyclization of unsaturated amides in high to excellent yields (80-94% isolated yields). Besides, the experiments of imaging of living cells were conducted to verify the proper fluorescence properties of the 2-oxazoline derivative. The results indicated that the probe had good cellular compatibility, as well as the potential to track spatial dynamics in living cells.

Design, Synthesis and Antifungal Activities of Novel Quinazolinone Derivatives

Plant pathogenic fungi have caused enormous yield and economic losses in agricultural production. In order to discover effective antifungal agents, a series of 19 novel quinazolinone derivatives 7 were designed and synthesized based on molecular splicing approach. The classical pharmacophore of amide was introduced into N-1 of quinazolinone skeleton. The structure was confirmed by ¹H NMR, ¹³C NMR and HRMS. Preliminary in vitro antifungal test showed that the target compounds exhibited moderate to favourable activities against six kind of plant pathogenic fungi at the concentration of 50 mg/L. Compound 7a had a significant inhibitory effect on Fusarium graminearum and Rhizoctonia solani, with EC₅₀ of 12.727 mg/L and 12.413 mg/L, respectively, which were better than chlorothalonil (14.323 mg/L and 13.339 mg/L). Molecular electrostatic potential of 7a indicated that the amide moieties located in the negative potential region and may generate hydrogen bond with target amino acid residue. The above results provided an effective strategy for the development of quinazolinone antifungal agents.

Development of 2-[(Pyridin-2-ylmethyl)thio]-1H-Benzimidazole Derivatives as Anticancer Agents: Design, Synthesis and Biological Activity

Benzimidazole is an important class of nitrogen-containing heterocyclic compounds, which has diverse biological activities. Herein, we reported a series of novel 2-[(pyridin-2-ylmethyl)thio]-1H-benzimidazole derivatives and evaluated their antiproliferative activities against human lung cancer A549, human colorectal cancer HCT116 and human prostate cancer PC3 cell lines with the MTT assay. Some target compounds demonstrated obvious antiproliferative activities against A549, HCT116 and PC3 cancer cell lines. Among them, 2-{3-{{2-{[(1H-benzimidazol-2-yl)thio]methyl}-3-methylpyridin-4-yl} oxy}propoxy}-1-(4-benzhydrylpiperazin-1-yl)ethanone (7c) showed the most potent antiproliferative activity with IC₅₀ values of 1.14 μM for A549, 1.67 μM for HCT116 and 2.34 μM for PC3, respectively. Preliminary structure-activity relationships were summaried and preliminary cellular mechanism studies elucidated that compound 7c could arrest the cell cycle at G₀/G₁ phase. The flow cytometry analysis showed that compound 7c could dose-dependently induce A549 cells apoptosis. Our studies suggested that the 2-[(pyridin-2- ylmethyl)thio]-1H-benzimidazole scaffold might be regarded as new scaffold structure for the development of potent cancer chemotherapeutic agents in the drug discovery process.

Ru(II)-Catalyzed Regioselective C-H Alkenylation of Indoles using Cyanomethyl Directing Group

Yan Fachao, Li Yang, Li Yudong, Mohamed Makha, Li Yuehui

Herein, we report a ruthenium-catalyzed C2-alkenylation of indole derivatives by employing cyanomethyl as the directing group for the first time. Site-selective alkenylation was achieved for a broad scope of alkenes as coupling partners with a large number of indoles bearing synthetically useful functional groups. The protocol represents a novel method for C2-alkenylation of indoles affording biologically relevant indolic compounds.

An Overview of the Reactions with Trifluoromethyl Trifluoromethanesulfonate

Long-Yu Ran, Cheng-Pan Zhang

Synthesis of fluorine-containing compounds is greatly dependent upon the development and application of fluorinated reagents. Thanks to the unique fluorine effects, fluorinated reagents usually exhibits different properties and reaction profiles from those of the non-fluorinated analogues. Among various trifluoromethoxylation reagents, trifluoromethyl trifluoromethanesulfonate has drawn much attention in recent years because of its easy preparation, low cost, and diverse reactivities. This reagent rapidly decomposes to form trifluoromethoxy anion in the presence of fluoride ion, thus regarding as a reservoir of trifluoromethoxy anion, and has been widely used in the nucleophilic trifluoromethoxylation reactions. Moreover, the trifluoromethoxy anion derived from trifluoromethyl trifluoromethanesulfonate and nucleophiles has poor thermal stability and tends to decompose at room temperature to afford fluorophosgene and fluorine anion, which could be used as a carbonylation reagent, a fluoroformylation reagent, a condensation agent, or a nucleophilic fluorination reagent. This review focuses on the trifluoromethoxylation, carbonylation, and fluorination reactions with trifluoromethyl trifluoromethanesulfonate as the reagent.

Synthesis of Dihydrobenzooxaphospholes via Cyclocondensation of 2-Phosphinylphenol and Aldehydes

Xueli Zhu, Shaoli Yang, Caixia Jia, Jing Li, Zheng Duan

A facile method to synthesize dihydrobenzooxaphospholes was developed from a p-toluenesulfonic acid (p-TSA)-promoted intermolecular cyclocondensation of the readily available 2-phosphinylphenol and aromatic aldehydes. The desired products were obtained as a mixture of stereoisomers. Interestingly, the diastereoisomers could be separated easily by flash column chromatography. The gram-scale and diastereoselective syntheses were also successfully performed.

Development of an efficient method for the synthesis of compounds containing P-O-P bonds: Pyrophosphonates, tetraalkyl pyrophosphates and pyrophosphonamidates

This work describes a method of synthesizing pyrophosphonates, tetraalkyl pyrophosphates and pyrophosphonamidates. Pyrophosphonates can be synthesized by the reaction of alkyl dichlorophosphonate, triethylamine (Et₃N), and water, in a ratio of 1:1.2:0.5 (dichlorophosphonate:Et₃N:water). When the reaction was allowed to proceed for 15 min in acetone, the maximum yield recorded for the pyrophosphonates was 95%. Et₃N was the solvent, with an acid-binding agent. Following this method, the achieved rate of production of tetraalkyl pyrophosphate and pyrophosphonamidate was faster than the rate of production of the compounds reached using traditional methods.

Phosphine-Catalyzed Synthesis of 1,3-Dihydro-3-alkylidene-2H-indol-2-ones

Li Jingjie, Wang Yuhao, Meng Tiantian, Huang Yiyong

The P(4-OMe-C₆H₄)₃-catalyzed Michael addition/double bond migration tandem reaction between allenyl imide and indol-2-ones is reported. This synthetic strategy for diverse 1,3-dihydro-3-alkylidene-2H-indol-2-ones features operationally simple, good substrate scope, high chemoselectivity and mild reaction conditions. The proposed reaction mechanism is also provided.

A New Germacrane-Type Sesquiterpene Lactone from Salvia castanea

One new germacrane-type sesquiterpene lactone, named as salviatanolide A (1) was isolated from an ethanol extract of the whole plant of Salvia castanea. Its structure was elucidated on the basis of 1D- and 2D-NMR and HRESIMS spectra, and the absolute configuration was determined by single-crystal X-ray crystallography. The anti-Alzheimer's disease (AD) activity of 1 was evaluated using humanized Caenorhabditis elegans AD pathological model. Compound 1 significantly delayed AD-like symptoms of worm paralysis phenotype, which may be potential to be served as anti-AD agent candidate.

Gradient enhancement of supramolecular organic framework for solubilization of hydrophobic molecules by two molecular containers in water

Many functional organic molecules have very low water-solubility, which remarkably limits their practical applications. The inclusion of water-soluble hosts has been demonstrated as an important strategy to increase the water solubility of organic molecules. However, this strategy usually requires high concentration for the hosts to realize efficient solubilization of guest molecules. Herein we report a new strategy of gradient solubilization by utilizing a water-soluble porous supramolecular polymer to adsorb or enrich molecular containers to increase their efficient concentration in a confined space. For this aim, a cationic water-soluble supramolecular organic framework was used to include an anionic calix[5]arene or an anionic acyclic cucurbituril. In this way, the supramolecular organic framework was revealed to exhibit significant gradient enhancement for the solubilization of the calix[5]arene host for C₆₀, C₇₀, ferrocene, 1,1'-dimethylferrocene and 1,1'-dibromoferrocene and the solubilization of the acyclic cucurbituril host for paclitaxel, docetaxel and cabazitaxel.

Synthesis of Nitrile via Electrochemical Appel Reaction

Haiqiong Li, Mengyun Yin, Fenfen Xie, Zhengbing Zhang, Pan Han, Linhai Jing

An electrochemical Appel reaction was developed for the synthesis of nitriles. This protocol features operationally simplicity, mild reaction conditions and environmental friendliness, enabling synthesis of various aromatic and aliphatic nitriles. Based on the controlled experiments and CV experimental results, an electrochemical Appel reaction mechanism was proposed to explain the reaction process.

Open-Air Stereoselective Synthesis of C-Aryl Fucosides/Arabinosides

Lai Meng-Nan, Wang, Qiu-Yuan, Hua Min, Huang Nian-Yu, Yao, Hui

Stereoselective construction of C-glycosylation is one of the research hotspots in carbohydrate chemistry field. An open-air stereoselective preparation of C-Aryl fucosides and arabinosides was reported using 3,4-O-carbonate glycals and arylboronicic acids based on a palladium-catalyzed decarboxylative allylation at ambient conditions and the configurations of products were determined by NMR, HRMS and X-ray single crystal diffraction analysis. Competitive reactions indicated that this approach has good compatibility with amino and alcoholic/phenolic hydroxyl groups. Further functionlization of unsaturated C-glycosides can be used to prepare a variety of C-glycosides. This mild method is simple in operation, wide application in substrate range, which provided a new idea for the rapid construction of carbohydrate library.

Synthesis and Antiproliferative Activity of 2,4,5,6-Tetrasubstituted Pyrimidine Derivatives Containing Anisole

In order to find efficient new anti-tumor drugs, a series of 2,4,5,6-tetrasubstituted pyrimidine derivatives containing anisole structure were designed, synthesized and evaluated for antiproliferative activity against four human cancer cell lines of PC-3, MGC-803, MCF-7 and HGC-27 using methyl thiazolyl tetrazolium (MTT) assay. Most of compounds displayed moderate to excellent antiproliferative activity against the four human tumor cell lines, among which the compound 5-ethyl-6-((4-methoxyphenyl)thio)-N⁴-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamine (14t) showed the best antiproliferative activity on HGC-27 cells, with IC₅₀value of (0.98 ± 0.12) μmol·L^-1, the antiproliferative activity is significantly better than that of the positive control 5-Fluorouracil. Further research on anti-tumor mechanism showed that compound 14t could significantly inhibit the colony formation and migration of HGC-27 cells and induce apoptosis. At the same time, compound 14t can down-regulate the expression of anti-apoptotic protein Bcl-2 and up-regulate the expression of pro-apoptotic proteins Bax and p53.

Recent Advance of Ketones Synthesis from Carboxylic Esters

Yi Wenjing, Sun Wei, Hu Xinquan, Liu Chao, Jin Liqun

Carboxylic esters are widely obtained, low-cost and readily available. Their conversions have attracted widespread attention. Ketones are important synthetic intermediates, which can be used to synthesize complicated drug molecules and functional materials with biological activity. In recent twenty years, great progress has been made in the synthesis of ketones from carboxylic esters. This review mainly covers the methods of converting carboxylic esters into ketones in recent years.

Two new 2,5-dioxopiperazines from the marine sponge Haliclona baeri

Wang Can-bin, Lei Yu, Liao Xiao-jian, Xu Shi-hai, Zhao Bing-xin

A series of secondary metabolites had been isolated from the sponge of genus Haliclona, most of which indicated antibacterial, cytotoxic and enzyme activities. However, few literatures about H. baeri had been reported before. In order to search more new bioactive marine natural products from this sponge, H. baeri had been studied systematically. Two new 2,5-dioxopiperazines, haliclines A (1) and B (2), together with five known ones (3-7), were isolated from the marine sponge Haliclona baeri. The structures of these compounds were elucidated by spectroscopic analysis. The absolute configurations of 1 and 2 were established by the method of ECD calculation. Compound 1 represented the first example of natural 2,5-dioxopiperazine bearing a L-azetidine-2-carboxylic acid moiety. The antibacterial activities of 1 and 2 were also evaluated.

Construction of Substituted N-phenylpyrazoles via a Catalyst-free and Additive-free Intermolecular Cyclization Process

A simple and practical protocol for the construction of substituted N-phenylpyrazoles was demonstrated from phenylhydrazine and pentane-2,4-dione under catalyst-free and additive-free conditions. The catalyst-free and additive-free process of operational simplicity, good functional group tolerance, step economy, scaled-up synthesis and high yields renders this strategy to be more useful in the synthesis of pyrazole drugs, biologically active molecules and pesticides.

Efficient Ultrasound-Assisted Approach to N-benzensulfonyl phenylacetamide via CuSO₄/NaAsc Catalysis in Water and Its Inhibition Activity of Seed Germination

Huang Zhi-You, Li Zhe-Zhi, He Bo, Li Wen-Sheng, Yang Ping, chen Li-Jun

Substituted phenylene and benzenesulfonyl-azide were used as starting materials to obtain N-benzensulfonyl phenylacetamide abscisic mimics(PACs). 32 target molecules were efficiently and quickly obtained via cheap combination of CuSO₄/NaAsc catalysis under ultrasonic radiation in water(86-95%). Furthermore, 22 novel mimics could overwhelmingly inhibit soybean seed germination at the concentration of 50 and 25 µM. These results are benefit to discovering novel seed germination inhibitor agents.

Research Progress of TRK Inhibitors

Yang Junzhe, Xu Zichao, Li Chunpu, cheng Yuanzheng, Liu Hong

TRK is a tyrosine kinase family activated by nerve growth factor, including TRKA, TRKB and TRKC, which are encoded by NTRK1 (Neurorosine receptor tyrosine kinase 1), NTRK2 and NTRK3 genes, respectively. After phosphorylation, TRK kinase can activate downstream signaling molecules, and then regulate cell proliferation, differentiation, metabolism and apoptosis. The NTRK gene can fuse with other genes, resulting in high kinase expression or continuous increase of kinase activity, leading to cancer. The main strategy for targeting NTRK fusion genes is to develop small molecule inhibitors of TRK that act on the intracellular kinase region. In recent years, the development of TRK small molecule inhibitors has also attracted the attention of researchers. This article reviews the structure, physiological function, TRK inhibitors and therapeutic strategies to overcome drug resistance of TRK kinase.

A High Photostability Mitochondrial Targeted NIR Dye with Large Stokes Shift and Cell Imaging Application

Zhou Hongmei, Tang Yonghe, Lu Huixu, Qian Zhang, Lin Weiying

Mitochondrial dysfunction is closely related to serious diseases such as Alzheimer's disease (AD), hypertension, diabetes and neurodegenerative diseases. The development of a fluorescent dye that can be highly targeted to mitochondria is essential for studying the physiological functions of mitochondria. However, the Stokes shift of the mitochondrial dyes on the market is very small and is easily affected by the self-absorption effect. Herein, we designed a new mitochondria targeted dye, named as Mito-ql, based on the properties of mitochondrial membrane potential. The dye Mito-ql has excellent optical properties such as large Stokes shift (about 165 nm), good chemical and photo stability, and low cytotoxicity. In addition, the cell imaging experiments demonstrated that the dye Mito-ql has excellent mitochondrial localization ability, which is not affected by changes in mitochondrial membrane potential.

A new turn-on fluorescent chemosensor for selective detection of Al³⁺ based on a purine Schiff base and its cell imaging

Ju Lixin, Shao qi, Lu Linchuan, Lu Hongfei

A new “turn-on” fluorescent probe (E)-2-((2-(8,9-di(naphthalen-1-yl)-9H-purin-6-yl)hydrazono)methyl)-5-(diethylamino)phenol (DNHP) for detecting Al³⁺ was designed, synthesized and evaluated based on purine Schiff base. The DNHP exhibited remarkable selectivity and rapid response towards Al³⁺ in MeOH/H₂O (v/v =9:1, pH = 7.4), accompanying with a slight color change from colorless to yellow. A good linear relationship (R²= 0.98367) was obtained between the emission intensity of DNHP and the concentration of Al³⁺ (2-6 µM) with a detection limit of 588 nM. The sensing mechanism of DNHP to Al³⁺ was supported by the Job's plot, ¹H NMR and density functional theory (DFT) study. More importantly, the sensor DNHP exhibits permeability and could be successfully applied for detection of intracellular cadmium ions in living HepG-2 cells.

Preparation of Imidazolium Ion Functionalized HG-II Chiral Ruthenium Catalysts and Their Catalytic Performance in Asymmetric Olefin Metathesis

The yield and stereoselectivity of the ruthenium-catalyzed olefin metathesis reaction are mainly determined by the nature of the ligands. In this study, two chiral HG-II ruthenium catalysts with imidazolium ion functionalized Hoveyda ligands were prepared and their activity and stereoselectivity in the symmetric ring-closure metathesis (ARCM) and asymmetric ring-opening cross-olefin metathesis (AROCM) reactions were investigated. The results show that the modification of the Hoveyda ligands by ionic functional group produced no significant effect on ARCM reaction; For AROCM reaction, ionic modification of the Hoveyda ligands shows an obvious improvment on both the E/Z selectivity and ee value for some products. Therefore, in the AROCM reaction, the Hoveyda ligands modified with imidazolium ion can be considered as a means to improve the stereoselectivity of the reaction.

Research Progress of Copper-Catalyzed Direct Vinylogous Reactions

Hui Li, Liang Yin

Vinylogous reaction serves as an efficient tool to introduce a new functional group at the γ-position (or even more remote position) of the parent functional group. The produced highly functionalized structure motifs (especially chiral ones) are ubiquitous in natural products, biologically active compounds, and pharmaceuticals. Moreover, they work as important synthetic intermediates in organic syntheses. Therefore, asymmetric vinylogous reaction has gained extensive attention in recent years. Our group is interested in the development of efficient direct vinylogous reactions by using copper catalysts with a focus on the catalytic asymmetric variants. Herein, advances in our group in this field are reviewed. Both α,β-unsaturated and β,γ-unsaturated compounds (including esters, aldehydes, ketones, phosphonates, sulfones, and nitriles) are used as the vinylogous pronucleophiles. Aldehydes, ketones, imines, and molecular oxygen are employed as the electrophiles. This account is divided into three sections based on the varied electrophiles: asymmetric vinylogous aldol reaction, asymmetric vinylogous Mannich reaction, and vinylogous aerobic oxidative hydroxylation. By using suitable copper catalysts, these reactions generally afforded the vinylogous products in good to excellent yields with good to excellent control of regio-, diastereo-, and enantioselectivities.

Magnetic Se/Fe/PCN-Catalyzed Oxidative Cracking Alkenes in O₂

Wenjian Zhou, Xinrui Xiao, Yonghong Liu, Xu Zhang

Oxidative cracking reaction of alkenes is not only applied in the synthesis of carbonyl compounds, but also in biomass conversion and degradation of organic pollutants. It is an organic chemical reaction with potential industrial application value. Developing a suitable catalyst to promote the reaction using molecular oxygen as a cheap and safe oxidant under mild conditions is a meaningful research topic in the interdisciplinary field of organic chemistry and material chemistry. In this work, we designed and prepared Se/Fe/PCN catalyst. The experimental results showed that the material was of excellent catalytic activity for the oxidative cracking of styrene derivatives. Notably, the selectivity of the reaction is good, and the selectivity of aldehydes in the product could reach 70-90%. The catalyst was magnetically separable, and could be reused for the next turn of reaction.

Organocatalytic Regio- and Enantioselective aza-1,8-Conjugate Additions of Isoxazol-5(4H)-ones to 6-Methide-6H-indoles

Wang Xing, Song Qianqian, Chen Xuling, Li Pengfei, Qi Yunkun, Li Wenjun

A chiral phosphoric acid catalyzed aza-1,8-conjugate addition of isoxazol-5(4H)-ones to 6-methylene-6H-indoles formed in situ from 6-indolylmethanols has been developed for the first time. Notably, the remote stereocontrolled 1,8-addition of isoxazol-5(4H)-ones was featured by N-selectivity, affording aza-adducts in 70-83% yield with 61-96% ee.

Asymmetric Photocatalytic Synthesis of Enantioenriched Azaarene Derivatives

Yin Yanli, Zhao Xiaowei, Jiang Zhiyong

The importance of azaarene derivatives in many arenas, especially pharmaceutical and material industry, has attracted increasing attention of chemists to develop highly efficient synthetic methods. To date, functionalization of commercially available azaarenes and their simple derivatives as feedstocks by exploiting the electronic properties of azaarenes to trigger transformations has been appreciated as a powerful tool. Among them, the methods via visible light-driven photocatalysis have been extensively explored, given the mild reaction conditions, good functional group tolerance and diverse reaction types. Notably, a number of asymmetric manifolds towards the synthesis of enantioenriched imine-containing azaarene derivatives have been established with satisfactory results. Here, we will summarize and discuss the advances of this important area. To enable readers to better understand the status of development, the main contents in this review are organized into four parts according to the relative positions of the formed stereocenters to azaarenes.

Synthesis of Chiral 5-Aryl-2-oxazolidinones via an Ir-BiphPHOX Catalyzed Enantioselective Hydrogenation

The enantioselective catalytic hydrogenation of 5-aryl-2-oxazolones has been achieved for the first time using the axially chiral Ir-BiphPHOX catalyst, which has been developed in our previous work, providing the corresponding chiral 5-aryl-2-oxazolidinones in high yields and with excellent enantioselectivities. The protocol has good compatibility with a variety of functional groups, and the resulting products can be converted into various chiral amino alcohol compounds or can be transformed into a series of chiral heterocyclic compounds with various biological activities.

Diterpenoid Alkaloids from the Roots of Aconitum rockii and their Antifeedant Activity

Shuai Huang, Yu-Ming Feng, Jia-Li Ren, Chuan-lun Yang, Lin Chen, Xian-li Zhou

As part of our ongoing research program toward discovering structurally intriguing and biologically important diterpenoid alkaloids from the Aconitum genera, four new diterpenoid alkaloids, including three C₁₉-diterpenoid alkaloids (rockidines A-C) and one C₂₀-diterpenoid alkaloid (rockisine A) were isolated from the roots of Aconitum rockii Fletcher et Lauener in this paper. Their structures were elucidated on the basis of spectroscopic analyses (HRESIMS, NMR and IR). All the new compounds (1-4), alone with ten known compounds (5-14) isolated in our previous work, were evaluated for their antifeedant activities, and compound 13 showed highly potent antifeedant activity with an effective concentration for 50% feeding reduction (EC₅₀) at 0.13 mg/cm².

Design, synthesis and cardioprotection of cryptotanshinone derivatives

Cryptotanshinone (CT) is the major lipid-soluble components of Salvia miltiorrhiza, which has myocardial protection and antioxidant effects. To improve its polarity, activity and targets, CT was designed and hybridized with salvianolic acids, the water-soluble active component in salvia miltiorrhiza, and its analogues at its 1 site. A total of 42 derivatives were synthesized, all of which are new compounds. Compared with CT, the polarity of the derivatives was improved. The cardioprotective effects of derivatives were preliminarily evaluated by Hypoxia/Reoxygenation injury (HRI) model in vitro. The results showed that the activity of most derivatives were enhanced compared with CT, especially compound 1R, 2R, 3S, 3R, 4R and 13S showed significant effects. SIRT1 high-throughput activity screening platform and molecular docking technology were used to explore the possible mechanism preliminarily. Structure-activity relationship studies showed that the product activity of 1-position R configuration was better than that of S-configuration, and the activity of aromatic acid derivatives with electron-donating substituents was better than that of with electron-absorbing substituents.

Synthesis of 1-[1-(Amino)cyclopropyl]ketones by Tandem Reaction Involv-ing Vinyl Selenium salt

A new one-pot method for the efficient synthesis of 1-[1-(amino)cyclopropyl]ketone compounds has been developed. Under the mediation of DBU, 1-[1-(amino)cyclopropyl]-ketones were obtained in 70% ~ 93% yields through a reaction sequence of nucleophilic addition/proton migration/nucleophilic substitution and deselenization of β-amino ketones and methyl phenyl vinyl selenium tetrafluoroborate. This method features mild reaction conditions, simple experiment operation, good functional group compatibility. Diphenyl diselenide, the general substrate of the selenium salt reagents, can be prepared by the simple treatment of the by-product methyl phenyl selenide with bromine and hydrazine. Therefore, the vinylselenide salts can be regenerated and reused, which improves the utilization of high-valent selenium reagents and improves the industrial application of this method.

A near-infrared fluorescent probe with 2-hydroxy-N,N-dimethyl- benzylamine as a new recognition fragment for Pd²⁺ detection and bioimaging

Zhang Xiangyang, Wu QingLin, Wang Feifei, Shen Youming, Tang Yucai

A near-infrared fluorescent probe DHDM bearing isophorone skeleton and 2-hydroxy-N,N-dimethyl- benzylamine has been rationally designed and synthesized. DHDM showed excellent Pd²⁺specificity, and it exhibited a low detection limit of 53 nM and a large Stokes shift (220 nm). The fluorescence intensity at 660 nm was linear to Pd²⁺ concentrations in a wide range（0-70 μM）. Additionally, a possible sensing mechanism was proposed based on the results of the mass spectroscopy, infrared spectrum, a comparative experiment and DFT calculations. Finally, DHDM was further successfully used to image Pd²⁺ in live cells, suggesting its potential applications in biological systems. The design strategy based on 2-hydroxy-N, N-dimethylbenzylamine or one of its analogues as a new recognition fragment will inspire researchers to construct privileged fluorescence probes in the future.

Metal-free Formation of 2-Substitued Benzoxazoles with Amides and Esters

Fangshao Li, Jing Xiao, Xiaofang Wu, Xiaoyi Wang, Jinfeng Deng, Zi-Long Tang

2-Substituted benzoxazoles are important heterocyclic motifs due to their wide application in pharmacology. We report a PCl₃-mediated C2-functionalization of benzoxazoles derivatives with inert amides and esters under metal-free conditions. By using PCl₃/I₂ combination, various 2-substituted benzoxazoles could be synthesized via the arylation or alkylation of benzoxazoles with amides and esters in the presence of water. What’s more, the reactivity between amides and esters was also investigated. The primary results indicated that amides have higher reactivity than esters under this system. This method features a broad substrate scope, simple condition and low-cost. A plausible mechanism was also proposed.

Direct Arylation of Benzoxazoles with ɑ-Keto Acids by Photoredox Catalysis

Li Yadong, Wu Pengju, Yang Zhiyong

An efficient protocol for arylation of benzoxazoles via visible light-initiation using Eosin Y as sole catalyst has been developed. The advantages of this methodology are mild reaction conditions and none metal catalyst was requested compared with the traditional condensation protocols leading to the similar products. The purification of the desired product is easier because only CO₂ is produced as the byproduct. Under the optimal reaction conditions, a wide range of benzoxazoles and ɑ-keto acids were tolerated.

Recent Progress in Benzylic C(sp³)-H Functionalization of Toluene and its Derivatives

Cai Chenyi, Zou Dong

Toluene derivatives are alkyl aromatic hydrocarbons derived from oil and natural gas and are among the cheapest and most readily available materials for the chemical industry. C-H functionalization is important for the synthesis of various bioactive substances, and inert benzylic hydrocarbon bond activation has long been a big challenge in this field due to the high hydrocarbon bond energy. Therefore, the development of simple and efficient methods for C-C and C-X bonds formation has been demonstrated as one of the hot topics by activating the benzylic C(sp³)-H bonds in recent years. In this review, the progress in benzylic C(sp³)-H functionalization of toluene and its derivatives under different catalytic conditions in the past decade is summarized according to different reaction classifications. The reaction substrate compatibility, mechanism, applications, advantages and limitations in this field are also discussed in detail.

Synthesis and Evaluation in vitro of Novel Harmine Derivatives as Anticancer Activity Agents

A series of novel 6-substituted harmine derivatives were synthesized from harmine in five steps: N⁹-methylation, bromination, suzuki coupling, N-Boc deprotection, and amidation reaction. The structures of target compounds were confirmed by ¹H NMR, ¹³C NMR, and HRMS. The in vitro antiproliferative activities were evaluated in a panel of cancer cell lines(HL-60, A549, SMMC-7721, MCF-7 and SW-480) via MTS assay. The results indicated that some compounds had good to excellent activities, and especially the most potent compound was 3o, whose IC₅₀ values were 0.27 (against HL-60), 0.44 (against A549) and 0.048μM (against SMMC-7721), better than positive control drugs cisplatin and taxol (against SMMC-7721).

Acidic zeolite HBeta catalyzed Friedel-Crafts alkenylation reaction

Liu Huili, Zhu Chaojie, Tang Tiandi

The Friedel-Crafts alkenylation of various alkynes and electron-rich arenes was achieved under mild conditions using acidic zeolite Hbeta as catalyst. HBeta possesses Lewis acid sites (LAS) and Bronsted acid sites (BAS), which are adsorption activation sites and protonation sites for alkynes, respectively. Preliminary studies have shown that the reaction proceeds through a BAS-promoted alkenyl cation process. The strong interaction between the alkenyl cation and BAS prevents the highly reactive alkenyl cation from polymerizing, avoiding the formation of oligomerized by-products. HBeta, as a heterogeneous catalyst, showed excellent reproducibility in the alkyne alkenylation reaction and could be recycled at least 5 times without significant loss of activity. Finally, according to the experimental results, the reaction mechanism of HBeta-catalyzed alkyne alkenylation was proposed.

Cobalt-catalyzed decarbonylative C8-acyloxylation of 1-naphthalamine derivatives with α-oxocarboxylic acids

Wang, Chaoyu, Dong, Shuda, Zhu, Tianyang, Liu, Yuqin, Wu, Zihan, Feng, Ruokun

The cobalt-catalyzed decarbonylative C8-acyloxylation of 1-naphthalamine derivatives with α-oxocarboxylic acids in the presence of Ag₂CO₃ and Na₂CO₃ was developed. Various substituted phenylglyoxylic acids, naphthalenylglyoxylic acid and 2-oxo-2-(thiophen-2-yl)acetic acid can be tolerated in this reaction, giving the desired products in moderate yields. In addition, an isotopic labeling aromatic esterification product was achieved in 62% yield when deuterated penylglyoxylic acid was employed.

Visible light induced arylfluoroalkylation of activated alkenes

Xinling Li, Weidong Meng, Xiu-Hua Xu, Yangen Huang

Fluorine-containing compounds have a wide range of applications in the fields of biomedicine and materials, and the development of synthetic methodology for fluorine-containing compounds is very important. Using fac-Ir(ppy)₃ as catalyst, a wide variety of amides containing fluoroalkyl substituted α-quaternary carbon center were prepared with N-phenyl-N-(phenyl sulfonyl) methyl acrylamide as starting material by visible light induced cascade fluoroalkyl radical addition, aryl migration and desulfonylation. The reaction conditions are mild, and possess good functional group compatibility.

Research Progress of ACQ-to-AIE Transformation Based on Organic Small Molecules

Most of the traditional organic fluorescent molecules have notorious aggregation-induced quenching (ACQ) effect, which limits their application in many fields. Therefore, how to achieve the transition from ACQ to aggregation-induced emission (AIE) while maintaining the functional properties of traditional conjugated molecules is of great significance. In recent years, many research groups have done a lot of breakthrough work in this field. According to the construction method and structural characteristics of AIE luminogen (AIEgen), the ACQ-to-AIE transformation strategy can be divided into two types. Based on the restriction of intramolecular motion (RIM) mechanism, the first one is to decorate ACQphore with typical AIEgen (e.g. tetraphenylethene unit). As the second one, some functional units (e.g. triphenylamine and cyanoethylene moiety) are introduced to realize the construction of AIE molecules from zero starting point as the RIM mechanism. In the latter, the construction of other AIEgen systems involving isomerism and ESIPT mechanisms has also been prominent recently. Thus, according to these classifications, the new progress on the construction strategy of ACQ-to-AIE transformation in the past five years is summarized from the four aspects of AIEgens' structure, performance, mechanism and application. In the future, to construct AIE molecules with diverse luminescence properties using a simple and green synthetic method and further expand their applications as promising directions should be highlighted.

Theoretical study on the catalytic mechanism of copper with various valence for the terminal alkyne coupling reaction

Copper-catalyzed homo-coupling reaction of terminal alkynes is of significant importance for the synthesis of conjugated diynes. Based on density functional theory and Marcus formula, this work reports the reaction mechanism for the copper-catalyzed homo-coupling reaction of phenylacetylene (PAY). Our calculations show that PAY is preferentially coordinated with the cuprous complexes in different organic solvents, which is transferred to Cu(II)-acetylide (complex 1) by single electron transfer reaction. Complex 1 is subsequently transferred to Cu(I)-acetylide (complex 2) by hydrogen elimination reaction. Another PAY is added to complex 2 forming complex 3, of which the terminal H is transferred intramolecularly. Followed by C_sp-C_sp coupling and ligand exchange reactions, the product 1,4-Diphenyl-1,3-butadiyne (DPBY) is obtained. Besides, the complex 3 could also become DPBY via subsequent intermolecular hydrogen elimination, C_sp-C_sp coupling, SET and ligand exchange reactions. In addition, under the strong base condition, phenylacetylene anion (PAY^-) is generated and then add to complex 2 forming complex 3'. Complex 3' then changes into complex 14 through disproportionation reaction, where the singlet-triplet coupling is involved. Complex 14 is dissociated into DPBY directly. The charges are computed for all the involved complexes, which are Cu(0)/(I) intermediates and Cu(II)/(I) transition states, illustrating the observed copper species with different valence in experiments.

Progresses in Reactive Fluorescent Probes with Fused AIE and ESIPT Structures

Guo, Yuetian, Pan, Yongxin, Tang, Lijun

Reactive fluorescent probes with the features of excited state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) have been widely used in the detection of various anions, metal cations and biomolecules in recent years, because they have some advantages including good biocompatibility, good sensing performance, a large Stokes shift, and as well high fluorescence quantum efficiency. This review briefly summarized the progress in reactive fluorescent probes that are structural simple and have the combined structures of AIE and ESIPT, and the probes are divided into several types such as benzothiazole, salicylaldehyde Schiff base, hydrazine dihydrazone, chalcone fluorophore, etc., and the related researches were discussed and prospected.

Synthesis and Electroluminescence of D-A type Near-Infrared Iridium (III) with Bipolar Features

Cao Liqin, Yang Xiaoqin, Li Maoqiu, Liu Lin, Yu Junting, Tan Hua

In this paper, an auxiliary ligand with bipolar transmission characteristics, namely pic-PSCz, was synthesized by covalently connecting electron transport diphenylsulfone (PS) unit and hole transport carbazole (Cz) unit to picolinic acid (pic), and a bipolar transmission donor-acceptor (D-A) type near-infrared iridium (III) complex (tBuTPA-BTz-Iq)₂Ir(pic-PSCz) was designed and synthesized (tBu is tert butyl, TPA is triphenylamine, BTZ is benzotriazole and Iq is isoquinoline). Compared with (Piq)₂Ir(pic-PSCz), there is about 110 nm red shifted of (tBuTPA-BTz-Iq)₂Ir(pic-PSCz) in emission spectra due to the strong D-A effect. Compared with the reported complex (TPA-BTz-Iq)₂Irpic, the photophysical and electroluminescent properties of (tBuTPA-BTz-Iq)₂Ir(pic-PSCz) were improved by introducing Cz and PS units. Its maximum emission peak is located in the near-infrared region of 716 nm, and a maximum external quantum efficiency (EQE_max) of 0.87% is achieved, which is three times as much as its parent complex (TPA-BTz-Iq)₂Irpic (EQE_maxis 0.29% @712 nm).

Configurational Assignment of Malfilamentoside A and a New Furanone Glycoside Malfilamentoside D

HPLC-DAD-based chemical analysis of the extract fraction library of the plateau soil-derived fungus Auxarthron umbrinum SCSIO 40432 led to the identification of eight compounds, including a known aromatic furanone glycoside malfilamentoside A (1) whose stereochemistry remained unsolved, and a new malfilamentoside D (2), together with six known compounds (3-8). The planar structures of malfilamentaoside A (1) and D (2) were elucidated by HRESIMS, 1D and 2D NMR spectroscopic analysis. The absolute configuration of malfilamentoside A (1) was unambiguously resolved for the first time by a single crystal X-ray diffraction analysis and the stereochemistry of malfilamentoside D (2) was determined by comparing ECD spectra of 1 and 2. Malfilamentoside A (1) exhibited inhibitory activity to xanthine oxidase at the concentration of 20 μM.

Dinorspongiapyridine, a New Dinorspongian Diterpene with Pyridyl D-ring from the Marine Sponge Spongia sp.

Chemical investigation of the marine sponge Spongia sp. led to a new dinorspongian diterpene dinorspongiapyridine (1) together with four known compounds (2-5). Compound 1 was the first instance of 3,4-seco-3,19-dinorspongian diterpene bearing a rare pyridyl D-ring system. The structure with absolute conﬁguration of 1 was elucidated by the methods of NMR and X-ray diffraction. In addition, the cytotoxic activities against several cancer cell lines of 1 were evaluated. The plausible biogenetic pathway of 1 was also proposed.

Modification Methods and Applications of Self-assembly Peptides

Ren Han, Li Ruxiang, Chen Zhijian, Li Lili, Wang Hao — 2021-05-25 00:00:00.0

Self-assembly peptide is a kind of peptide material that can form assembly under certain conditions due to the intermolecular forces such as π-π stacking and electrostatic interaction. This class of material exhibits good biocompatibility and controllability, and can form nanostructures such as granules, fibers and gels, which play a specific morphologic function and are widely used in biomedicine and other fields. In order to meet the needs of drug delivery, disease diagnosis and regulation of hydrophilic hydrophobic balance of peptides, it is necessary to perform modification for peptides. Due to the assembly characteristics of peptides and their biological functions, modified peptides have more advantages than the unmodified ones. Thus, functional modification for self-assembly peptides has been investigated intensively in recent years. The modification sites in peptide are usually the carboxyl and amino groups at both ends, as well as the active groups on the amino acid side chain. However, it is difficult for some molecules to react with peptides directly. Accordingly, two modification methods, i.e. direct and indirect modifications, have been developed in research. In this paper, the recent functionalization methods of self-assembly peptides and relevant applications are reviewed.

Progress in Design and Application of Supramolecular Fluorescent Systems Based on Difluoroboron-dipyrromethene and Macrocyclic Compounds

Guo Jingjing, Guo Minjie* — 2021-05-25 00:00:00.0

Macrocyclic compounds play an important role in supramolecular chemistry because of their unique shape, reactivity and host-guest properties. Cyclodextrin, calixarene, calixpyrrole, cucurbituril and pillararene are the most common macrocyclic compounds. In addition, many new macrocyclic molecules have been reported in recent years. Difluoroboron-dipyrromethene (BODIPY) dyes are widely used in biological and chemical fields because of their excellent optical properties, including narrow absorption and fluorescence emission bands, high molar absorption coefficient, high quantum yield and good light, thermal and chemical stability. The combination of macrocyclic compounds and BODIPY dyes has been proved to be an effective strategy for the construction of smart materials with specific properties. In this review the macrocyclic compounds containing BODIPY reported in recent years have been summarized and discussed based on the functional application and the future development direction in this field was put forward.

Research Progress of Aryltriazene as Aryl Precursor and Aryl-azo Precursors in Organic Synthesis

Zhang Yonghong, Tang Chengzong, Liu Yonghong, Liu Chenjiang — 2020-12-05 00:00:00.0

Aryltriazenes have emerged as very useful and versatile building blocks in organic synthesis due to their easy preparation, good stability, multiple reaction sites and mild reaction conditions. In this review, the recent advances in the application of aryltriazenes in organic synthesis as aryl or aryl azo precursors are reviewed.

Three-component one-pot synthesis of novel 1,5-benzodiazepine derivatives and their anti-BVDV activity

2020-09-30 00:00:00.0

The "one-pot" three-component reaction is established to synthesize 1,5-benzodiazepine derivatives containing pyrrolidinone. These reactions were carried out readily with p-toluenesulfonic acid (p-TSA) as the catalyst in good yields. Reaction conditions were mild, environmental friendly. The benzodiazepine derivatives displayed prominent anti-BVDV activity with excellent EC₅₀ values and no significant cytotoxicity. Our research could afford significative compounds for the research of anti-BVDV agents.

Design, Synthesis and Anticancer Activity Studies of Novel Indole-Pyrimidine Biaryl Derivatives

Dan-Qing Zhang, Xu Liu, Xiao-Jing Pang, Hong-Min Liu, Qiu-Rong Zhang — 2020-09-16 00:00:00.0

A series of novel indole-pyrimidine biaryl derivatives were designed, synthesized and evaluated for inhibitory activity against LSD1 and antiproliferative activity against five selected cancer cell lines (MGC-803, PC-3, EC-109, PC-12 and MCF-7). The priliminary structure-activity relationship (SAR) for this indole-pyrimidine biaryl scaffold is explored in this report with evaluation of 22 variants of the structural class. Among these analogues, compound 6i exhibited the potential inhibitory activity against LSD1 (IC₅₀=1.03 µM), compounds 6c, 6f and 6k showed the potential inhibitory activity aginst PC-3 cells. Especially, compound 6k exhibited the best antitumor activity (IC₅₀=2.75 µM), which was served as bioactive fragment and hit compound for developing more potent antitumor agents.

Ruthenium(II)-Catalyzed Synthesis of N-Heterocycles via Acceptorless Dehydrogenative Condensation

2020-08-01 00:00:00.0

Four bidentate ruthenium(Ⅱ) complexes 1-4 were tested as catalysts for the synthesis of quinolines via acceptorless dehydrogenative condensation (ADC) strategy, using o-aminobenzyl alcohol and ketones as the starting materials, and complex 4 exhibited the highest activity. With 0.3 mol% catalyst loading and 1.0 equivalent of KOH, 26 quinoline derivatives were isolated in high yields within 2 hours at 120℃. Moreover, under similar conditions, this multifunctional catalyst is also applicable for the preparation of other N-heterocycles, and a series of naphthyridines, pyridines and pyrroles were generated.

The effect of structure modification of benzothiadiazole acceptor unit on the D-A-D-A-D typed oligothiophene based donor materials for organic small molecules solar cells: A theoretical study

Lihui Wang, Suozhu Bai, Dongyong Li, Hong Zhou — 2019-11-08 00:00:00.0

Four D-A-D-A-D structured organic small molecules (OSMs) DOBT-8T, BT-8T, FBT-8T and FFBT-8T has been designed for organic solar cells, which contains tetrathiophene as the core donor unit, bithiophene as the termial donor unit, combining different electron-withdrawing fragments DOBT, BT, FBT and FFBT as acceptor unit, respectively. The designed four OSMs are analyzed using density functional theory (DFT) and time dependent-DFT (TDDFT) calculations at B3LYP /6-31G(d) level. The effects of structure modification of benzothiadiazole acceptor unit on modulating the electron-donating ability of OSMs were fully investigated. Re-sults showed that the geometrical structure, the band-gap, HOMO/LUMO energy levels, orbital spatial distribu-tion, energetic driving force, open-circuit voltage and NPA atomic charge of these OSMs can be systematically al-tered by varying the electron-withdrawing properties with different benzothiadiazole acceptor units. Compared to other OSMs, FBT-8T displayed the more narrowed Eg and relatively deeper HOMO level with FBT as acceptor. FFBT-8T exhibited the most deep-lying HOMO level of the four designed OSMs and suitable Eg value by using FFBT as acceptor. The power conversion efficiencies (PCEs) of ~4.7% and ~5.2% were achieved by the photo-voltaic devices based on FBT-8T:PC61BM and FFBT-8T:PC61BM system, respectively, predicting with Scharber models. On the basis of these results, we propose FBT-8T and FFBT-8T as potential OSMs donor materials for high-efficiency organic bulk hetero-junction solar cell.

A Facile and New Synthetic Method of Polysubstituted Furans

Zou Wen, He Zheng-Rong, He Zhengjie — 2015-04-03 00:00:00.0

With the treatment of tributylphosphine and base, alkynoates, aromatic aldehydes and acyl chlorides readily undergo a four-component cascade annulation reaction, giving tri- or tetrasubstituted furans in moderate yields. The reaction presumably proceeds through an intramolecular Wittig reaction step of the in situ generated phosphorus ylide intermediate. The annulation reaction features mild reaction conditions and broad substrate scope, and accordingly constitutes a facile and new synthetic method of polysubstituted furans.

Cu-Catalyzed Synthesis of Novel Benzo[e]pyrazolo[1,5-c][1,3]thiazine Derivatives

Li Ming, Zhang Jianwei, Wen Lirong — 2014-09-09 00:00:00.0

Based on substrate-design concept, a high chemoselectivitive synthetic strategy of novel benzo[e]pyrazolo[1,5-c][1,3]thiazine compounds through the Cu-catalyzed reactions of 5-(2-bromoaryl)-1H-pyrazol-3-amines and isothiocyanates was developed by using 1-(2-bromoaryl)-3-ethoxy-3-amino)prop-2-en-1-ones as raw material, which has advantages of simple operation, mild reaction conditions, and high yields.

The Hydroxyla(Acyla)tion of Purpurin-18 imide and Synthesis of Chlorophyllous Chlorins Derivatives

JI Jian-Ye, YIN Jun-Gang, ZHAO Li-Li, YAO Nan-Nan, QI Cai-Xia, WANG Jin-Jun — 2014-07-15 00:00:00.0

Purpurin-18 methyl ester, as a starting material, was converted into purpurin-18 imide linked substituted structures bearing hydroxyl or acyl group at nitrogen atom in the imide by aminolysis for exocyclic ring. The hydroxyl, acyl or substituted groups with relevant functional structures were introdued by oxidation, allomerization, radical substitution and nucleophilic substitution reaction making use of active reactive regions on the periphery. The synthesis of 12 unreported chlorophyllous chlorins with carbon skeleton of purpurin-18 imide were accomplished and their chemical structures were characterized by elemental analysis, UV, IR and ¹H NMR spectra. The different effects on the tetrapyrrol macrocycle by hydroxylation and acylation were discussed.