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The nucleophilic aromatic substitution (SNAr) between heteroaryl halides (Cl, Br) and thiols proceeds smoothly in DMAc under the action of K2CO3at rt–100 °C. For most electron-deficient heteroarenes, reaction takes place without introducing an additional electron-withdrawing group. For electron-rich heteroarenes, an additional electron-withdrawing group such as a simple ester, keto, cyano, and nitro group is required to ensure the reaction completes. The reactivity trend of heteroaryl halides is highly dependent on the electronic nature of the heteroarenes and orientation of halogens. Besides thiols, a couple of functionalized thioureas and thioamides are compatible with these conditions, providing the corresponding heteroaryl thioethers in good yields.

The N,N'-bis(thiophen-2-ylmethyl)oxalamide (BTMO) was found to be an effective ligand for Cu-catalyzed ipso-nitration of (hetero)aryl halides (Br, I), making the coupling reaction with sodium nitrite proceed smoothly at 100–120 °C with 1–5 mol % CuI and BTMO. Electron-rich substrates were the best coupling partners to give the desired coupling products in good to excellent yields at 100 °C. Electron-neutral substrates required heating at 120 °C to get complete conversion, while rather low conversions were observed in the case of electron-poor (hetero)aryl bromides.

The duality of function (cell cycle regulation and gene transcription) of cyclin-dependent kinase 7 (CDK7) makes it an attractive oncology target and the discovery of CDK7 inhibitors has been a long-term pursuit by academia and pharmaceutical companies. However, achieving selective leading compounds is still difficult owing to the similarities among the ATP binding pocket. Herein, we detail the design and synthesis of a series of macrocyclic derivatives with pyrazolo[1,5-a]-1,3,5-triazine core structure as potent and selective CDK7 inhibitors. The diverse manners of macrocyclization led to distinguished selectivity profiles of the CDK family. Molecular dynamics (MD) simulation explained the binding difference between 15- and 16-membered macrocyclic compounds. Further optimization generated compound 37exhibiting good CDK7 inhibitory activity and high selectivity over other CDKs. This work clearly demonstrated macrocyclization is a versatile method to finely tune the selectivity profile of small molecules and MD simulation can be a valuable tool in prioritizing designs of the macrocycle.

It is significant to reduce power consumption and thickness of foldable display with larger size. Color filter on Encapsulation (COE), as one of the most critical technologies, has excellent performance in terms of power consumption and thinning. COE refers to the technical proposal replacing polarizer with color filter on the surface of encapsulation(COE). However, we have encountered two problems of reduced mechanical strength in the mass production. One of the problems is panel peeling in module process, and the other one is cracking during drop test. This paper has studied the root cause of COE panel strength reduction from panel design, process and material. As a result we achieved the same mechanical strength as polarizer panel.

There is a bad performance in the image quality of AMOLED display, which is the graininess and the non‐uniformity brought by the graininess. This phenomenon is called Sandy Mura in this paper. After systematic research and analysis, Sandy Mura is divided into three types. These three types of Sandy Mura interfere with each other in observation and judgment, making adverse improvement extremely difficult. In this study, the main elements for several Sandy mura types were experimentally verified, and their distinct mechanisms and models were developed. According to the models, the improvement plan was proposed. After a series of improvements, Sandy mura was finally effectively improved.

The napelline-type alkaloids possess an azabicyclo[3.2.1]octane moiety and an ent-kaurane-type tetracyclic skeleton (6/6/6/5) along with varied oxidation patterns embedded in the compact hexacyclic framework. Herein, we disclose a divergent entry to napelline-type alkaloids that hinges on convergent assembly of the ent-kaurane core using a diastereoselective intermolecular Cu-mediated conjugate addition and subsequent intramolecular Michael addition reaction as well as rapid construction of the azabicyclo[3.2.1]octane motif via an intramolecular Mannich cyclization. The power of this strategy has been demonstrated through efficient asymmetric total syntheses of eight napelline-type alkaloids, including (−)-napelline, (−)-12-epi-napelline, (+)-dehydronapelline, (+)-12-epi-dehydronapelline, (−)-songorine, (−)-songoramine, (−)-acoapetaldine D, and (−)-liangshanone.

Cu-mediated Ullmann-type cross-coupling has experienced significant advances over the last century since the seminal publication by Ullmann in 1901. These advances have significantly expanded the scope of the original classical Ullmann coupling of aryl halides for formation of diaryl compounds to include the formation of carbon–heteroatom and other carbon–carbon bonds. The introduction of bidentate ligands drastically improved the performance of this class of transformations to enable milder reaction conditions that can tolerate a wide range of sensitive functional groups. Recent development of more powerful second-generation bidentate ligands has further allowed the coupling of less reactive aryl chlorides to proceed smoothly and realized low catalyst and ligand loadings for a broad scope of Ullmann-type cross-coupling reactions. As a result of these breakthrough advances in the past decades, Cu-mediated Ullmann-type cross-coupling reactions have been frequently implemented in academic research and have found ubiquitous industrial applications including the preparation of pharmaceutical and agrochemical products. This review provides an overview of selected general Cu-mediated Ullmann-type transformations for the formation of carbon–carbon and carbon–heteroatom (C–N, C–O, C–S, and C–P) bonds and their applications in route design, process development, and scale-up of pharmaceutical and agrochemical processes.

N,N′-Bis(pyridin-2-ylmethyl)oxalamide (BPMO) was found to be an apposite promoter for the Cu-catalyzed N-arylation of oxazolidinones and primary and secondary amides with (hetero)aryl iodides at room temperature. Excellent chemoselectivity reached between aryl iodides and aryl bromides, and a wide range of functional groups tolerated the reaction conditions, which led to the formation of greatly diverse N-arylation products.

With the rapid development of new energy power plants (NPPs) in China, installation of energy storage facilities (ESFs) and flexibility improvement of conventional coal-fired power plants (CPPs) are encouraged by government to provide auxiliary service. Compared with flexibility retrofitting, configuration of ESFs may be feasible to improve the flexibility and adaptation of outdated CPPs, which is more sensitive to the investment and economic returns. This study explores the technical and economic features of battery ESFs in a group of conventional CPPs and makes a comparison in three types of modes, including the mode without ESFs, modes with ESFs for their own use, and modes with shared ESFs. An optimization model is established and employed to obtain the best installed capacity and corresponding sharing ratio of ESFs. The optimization results of multiple modes show that ESFs will improve flexibility of CPPs and penetration rate of new energy in general. If the ESFs can be shared between CPPs and NPPs, not only the Equivalent Available Factor (EAF), but also the annual net profit of ESFs will be increased. According to the results of a numerical simulation, CPPs will get the highest net profit if the installed ESFs can be shared with a proportion of 50 %–75 %. This research can contribute to optimizing the configuration and operation of shared ESFs invested by conventional CPPs, and improving cooperation mechanisms of ESFs in the new power system.

To overcome the limitations of traditional desulfurization wastewater treatment in coal-fired power plants that entail complicated processes and high chemical consumption, we propose a novel in situ gelation treatment combining flocculation and adsorption using alginate without additional cross-linking agents. Metal ion pollutants in desulfurization wastewater were employed as cross-linkers to gelate biomacromolecules of alginate resulting in the simultaneous formation of hydro-gels and the removal of pollutants. The results show that alginate can effectively utilize the metal ions in desulfurization wastewater, which are instantaneously gelated into hydrogels, resulting in flocculation and adsorption. An alginate dosage of 12 g/L and a reaction time of 3 h were identified as the optimum reaction conditions. Alginate was modified using 1,3,5-triazine-2,4,6-trithiol trisodium salt, ethylenediamine and thiosemicarbazide to enhance its contact with metal ions. The results demonstrate that the optimum treatment effect was obtained using ethylenediamine at 0.02 g/L, with removal rates of 71.1%, 70.8%, 64.1% and 65.0% for Ca, Cr, Cd and As, respectively. The method proposed here is easy to operate and with low cost, suggesting broad prospects for application in industrial wastewater treatment.

The field of total synthesis has reached a stage in which emphasis has been increasingly focused on synthetic efficiency rather than merely achieving the synthesis of a target molecule. The pursuit of synthetic efficiency, typically represented by step count and overall yield, is a rich source of inspiration and motivation for synthetic chemists to invent innovative strategies and methods. Among them, convergent strategy has been well recognized as an effective approach to improve efficiency. This strategy generally involves coupling of fragments with similar complexity to furnish the target molecule via subsequent cyclization or late-stage functionalization. Thus, methodologies that enable effective connection of fragments are critical to devising a convergent plan. In our laboratory, convergent strategy has served as a long-standing principle for pursuing efficient synthesis during the course of planning and implementing synthetic projects. In this Account, we summarize our endeavors in the convergent synthesis of natural products over the last ten years. We show how we identify reasonable bond disconnections and employ enabling synthetic methodologies to maximize convergency, leading to the efficient syntheses of over two-dozen highly complex molecules from eight disparate families.

Cu2O/N,N′-bis(thiophen-2-ylmethyl)oxalamide is established to be an effective catalyst system for Goldberg amidation with inferior reactive (hetero)aryl chlorides, which have not been efficiently documented by Cu-catalysis to date. The reaction is well liberalized toward a variety of functionalized (hetero)aryl chlorides and a wide range of aromatic and aliphatic primary amides in good to excellent yields. Furthermore, the arylation of lactams and oxazolidinones is achieved. The present catalytic system also accomplished an intramolecular cross-coupling product.

A general and practical catalytic system for aryl amination of aryl chlorides with aqueous or gaseous ammonia has been developed, with CuI as the catalyst and bisaryl oxalic diamides as the ligands. The reaction proceeds at 105–120 °C to provide a diverse set of primary (hetero)aryl amines in high yields with various functional groups.

In our pursuit of sustainable and reliable Smart Cities Energy Hubs, we employ Digital Twin technology for precise modeling. Focusing on CHP known as combined heat and power for the energy hubs, we address winter heat load challenges while integrating renewable energy within UEN as unified energy networks. Power IoTs known as PIoTS which is known as the Power Internet of Things, facilitates seamless data transmission, enhancing UEN flexibility and renewable energy accommodation. Using Covariance Matrix Adaptation Evolution Strategy, this research optimizes UENs within PIoTs’ framework. We develop a digital twin incorporating combined demand response (DR) and essential UEN components. Formulating a bi-level economic dispatching process via PIoTs and UEN, our approach optimizes total UEN function and demand-side equipment output using Covariance Matrix Adaptation Evolution Strategy known as CMA-ES. Testing against standard and practical UEN models validates our method’s efficiency. Through Digital Twin modeling and CMA-ES, our study revolutionizes Smart Cities Energy Hub development, offering a sustainable path forward.

N,N′-Dibenzyloxalamide (DBO) was identified as a powerful ligand for promoting Cu-catalyzed coupling of heteroanilines with (hetero)aryl halides. For (hetero)aryl chlorides, the coupling reaction occurred at 130 °C with 5 mol % CuBr and 10 mol % DBO. For (hetero)aryl bromides/iodides, coupling reaction took place at 80–100 °C with 1 mol % CuI and 2 mol % DBO. A variety of heteroanilines worked well to afford the arylation products in good to excellent yields.

A robust and practical protocol for preparing alkyl aryl ethers has been developed, which relies on using two types of ligands to promote Cu-catalyzed alkoxylation of (hetero)aryl halides. The reaction scope is very general for a variety of coupling partners, particularly for challenging secondary alcohols and (hetero)aryl chlorides. In case of coupling with aryl chlorides and bromides, two oxalic diamides serve as the powerful ligands. The tert-butoxide is first demonstrated as a ligand for Cu-catalyzed coupling reaction, leading to alkoxylation of aryl iodides complete at room temperature. Additionally, a number of carbohydrate derivatives are applicable for this coupling reaction, affording the corresponding carbohydrate-aryl ethers in 29–98% yields.

A concise approach to synthesize the tetracyclic framework of the marine diterpenoid plumisclerin A is described. Starting from commercially available iridoid genipin, a highly selective intermolecular Diels–Alder reaction was utilized to construct the A/B/C tricycle. Later, a four-step sequence involving stereoselective epoxidation and Dauben oxidative rearrangement was developed to introduce the requisite enone moiety. The unique tricyclo[4,3,1,01,5]decane motif was successfully forged via a late-stage SmI2-mediated reductive coupling.

The gelsedine-type alkaloids possess a common oxabicyclo[3.2.2]nonane core and spiro-N-methoxyindolinone moiety along with a diversely functionalized heterocycle embedded in the compact framework. Herein we disclose a divergent entry to gelsedine-type alkaloids that hinges on rapid assembly of the common core by the orchestrated application of an asymmetric Michael addition, a tandem oxidation/aldol cyclization, and a pinacol rearrangement and generation of the structural diversity via a late-stage heterocyclization. The power of this strategy has been demonstrated through very short total syntheses of four gelsedine-type alkaloids: gelsedilam, gelsenicine, gelsedine, and gelsemoxonine.

N1-(2,6-Dimethylphenyl)-N2-(pyridin-2-ylmethyl)oxalamide (DMPPO) was revealed to be a more effective ligand for copper-catalyzed coupling reaction of (hetero)aryl halides with 1-alkynes than previously reported ones. Only 3 mol % CuCl and DMPPO are required to make the coupling complete at 100 °C (for bromides) and 80 °C (for iodides). Both (hetero)aryl and alkyl substituted 1-alkynes worked well under these conditions, leading to the formation of internal alkynes in great diversity.

Honeycomb sandwich panels (HSP) have exhibited significant advantages in light weight and energy absorption, and they have been widely applied in the automotive, aerospace, transportation and defense industries. Rather than restating details of the existing standard regular hexagon HSP (R0-HSP), this paper introduces single-rib reinforced regular hexagon HSP (R1-HSP) and double-rib reinforced regular hexagon HSP (R2-HSP). The mechanical characteristics of these three structures are first investigated by series full-scale elaborator models through LS-DYNA. It is found that the R1-HSP has the best crashworthiness performance under axial impact regarding specific energy absorption per unit (SEAmand SEAv) when the peak crashing stress (σpeak) is less important. Secondly, the thickness matching effect between stiffener and cell wall is analyzed with equivalent apparent density index to evaluate the contribution of the change of deformation model to the general mechanical properties. Consequently, stiffener thickness of 2.0 times and 1.5 times that of cell wall are found to be the most optimal options for R1-HSP and R2-HSP, respectively. To optimize the crashworthiness of the R1-HSP, optimal Latin hypercube design method is used for selection of sampling design points in the design space. And in the meantime, an accurate surrogate modeling method, or more specifically named as response surface method, is adopted to formulate the SEAm, SEAvand σpeakfunctions. The results yielded from the optimization indicate that the R1-HSP is superior to R0-HSP both in SEAmand SEAvunder the same limitation of σpeak. This research is significant in providing technical support in the extended applications of different HSPs used as crashworthiness structures, and it has essential reference value in low volume and low mass energy absorber design.

In this article, a practical method named feedback nonlinear robust control with disturbance compensation is proposed for a hydraulic system with matched and mismatched generalized uncertainties (e.g. parameter derivations, external disturbances, modeled errors and/or unmodeled dynamics), in which a finite-time disturbance observer and a nonlinear robust controller are integrated together by backstepping method. The finite-time disturbance observer is used to estimate matched and mismatched generalized uncertainties. The design of the nonlinear robust controller is to make the closed-loop system stable. Not only the nonlinearities (e.g. nonlinear flow features of servo-valve) but also matched and mismatched generalized uncertainties are considered by the proposed controller. Furthermore, asymptotic output tracking performance after a time T0is theoretically ensured by the proposed controller. The high-performance nature of the proposed control strategy is verified by extensive comparative experimental results.

An organocatalytic Michael addition of protected 2‐amino‐1‐nitroethanes to α,β‐unsaturated aldehydes followed by treatment with TFA afforded 4‐substituted 3‐nitro‐1,2,3,4‐tetrahydropyridines with good diastereoselectivity and excellent enantioselectivity. Good yields were observed in the case of β‐aryl‐substituted α,β‐unsaturated aldehydes as the substrates, while moderate yields were obtained when β‐alkyl‐substituted α,β‐unsaturated aldehydes were used.

So einfach wie A, B: Die ersten Totalsynthesen der (−)‐Communesine A und B (siehe Bild) wurden fertiggestellt. Die Synthese des spiro‐verknüpften Indolin‐Teils erfolgte über eine intramolekulare oxidative Kupplung und die des A‐Rings in einer Kaskadenreaktion.

O‐Trimethylsilyl (TMS)‐protected diphenylprolinol‐catalyzed Michael addition of a functionalized alkylidene malonate and n‐butanal affords an aldehyde. This adduct can serve as the common intermediate for the assembly of secologanin tryptamine and dopamine alkaloids; this is demonstrated by the total syntheses of corynantheidol, dihydrocorynantheol, protoemetinol, and protoemetine, and the formal synthesis of mitragynine. The key steps include reductive amination of this aldehyde with tryptamine, condensation of this aldehyde with 4‐methoxytryptamine, condensation of dimethoxyphenethylamine with a lactone derived from this aldehyde, and subsequent Bischler–Napieralski cyclization and reduction.

Condensation of (S)‐3‐aminobutan‐1‐ol with 1,3‐cyclohexane‐dione followed by an intramolecular alkylation afforded bicyclic enamine 32, which was converted into enone 35through a diastereoselective hydrogenation. Mukaiyama–Michael addition of a bicyclic silyl enol ether to 35and subsequent stereochemistry inversion by means of an oxidation/reduction strategy provided lactone 41. After reduction of lactone 41with LAH, Swern oxidation was carried out to give enone 46upon a spontaneous intramolecular aldol reaction and cleavage of the ketal protecting group. SmI2‐mediated carbonyl–alkene reductive coupling of 46proceeded smoothly in refluxing tetrahydrofuran to deliver pentacyclic intermediate 49, which was oxidized with 2‐iodoxybenzoic acid and then treated with trifluoroacetic acid to furnish (−)‐GB 13. The overall yield was 6.1 % over 19 linear steps. By following the known procedure, our synthetic (−)‐GB 13 was converted into himgaline. In addition, by starting from lactone 41, the first total synthesis of (+)‐GB 16, a newly isolated member of the gabulimima alkaloid family, was achieved. This synthesis features an intramolecular condensation between an amine and a 1,3‐diketone moiety.

All in it together: A highly efficient and extremely versatile method for the assembly of benzothiazoles with a nitrogen substituent in the 2‐position relies on a copper‐catalyzed cascade reaction of a 2‐haloaniline, carbon disulfide, and an N nucleophile (see scheme). The products are useful precursors for the synthesis of a range of important pharmaceutical agents. DMF=N,N‐dimethylformamide; R,R′=H, alkyl, aryl; Z=Me, CF3, CO2Me, CN, N2O, Cl, F, Ac.

Alles dreht sich um Alkaloide: Eine 19‐stufige Totalsynthese des Galbulimima‐Alkaloids (−)‐GB 13 ausgehend von kommerziell erhältlichen Verbindungen und die erste Totalsynthese des Galbulimima‐Alkaloids (+)‐GB 16 werden beschrieben (siehe Schema; Boc=tert‐Butoxycarbonyl).

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Hey Mickey, you're so fine!Organocatalytic Michael additions of aldehydes with protected 2‐amino‐1‐nitroethene could go through three different transition‐states to afford adducts with usual and unusual stereochemistry, thereby providing a facile entry to Tamiflu (see scheme) and substituted 3‐aminopyrrolidines. TMS=trimethylsilyl, Ac=acetyl.

The golden touch: Total synthesis of natural (−)‐englerin A from (R)‐citronellal has been achieved using a gold‐catalyzed cyclization as the key step (see scheme). No protecting‐group manipulations were required in the synthetic sequence.

Doppelte Verknüpfung: Eine allgemeiner und effizienter Syntheseansatz für substituierte Phenothiazine nutzt eine CuI/L‐Prolin‐katalysierte Reaktionskaskade, die in kontrollierter Weise eine C‐S‐ und eine C‐N‐Bindung aufbaut.

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Autophagy functions as an important catabolic mechanism by mediating the turnover of intracellular organelles and protein complexes. Although the induction of autophagy by starvation has been extensively studied, we still understand very little about how autophagy is regulated under normal nutritional conditions. Here we describe a study using a small molecule autophagy inducer, fluspirilene, as a tool to explore the mechanism of autophagy induction in normal living cells. We confirm the activity of fluspirilene in inhibiting Ca2+flux. Furthermore, we show that reducing intracellular Ca2+prevents the cleavage of ATG5, which in turn increases the levels of full-length ATG5 and ATG12-ATG5 conjugate. Using siRNA mediated gene silencing, we demonstrate that inhibiting calpain1 is sufficient to induce autophagy in living cells. We conclude that calpain1 plays an important role in controlling the levels of autophagy in normal living cells by regulating the levels of a key signaling molecule, ATG12-ATG5 conjugate.

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The first example of an organocatalytic asymmetric Michael addition of aldehydes to α,βunsaturated thiol esters promoted by chiral diphenylprolinol silyl ether is presented. The reaction occurs with good yields, diastereoselectivity and excellent enantioselectivity.

Making circles with N and O: Cyclic tripeptides containing an unnatural Cα‐tetrasubstituted THF amino acid are prepared by copper(I) and palladium(0)‐catalyzed N‐ and O‐arylation reactions. The reactions give access to side chain‐modified derivatives of the unnatural amino acid and macrocyclic peptidomimetics.

Mit einfachsten Mitteln: Die erste metallkatalysierte direkte Kupplung zwischen Metallsulfiden und Arylhalogeniden mit anschließender intramolekularer Kondensation ergab substituierte Benzothiazole siehe Schema. Zahlreiche funktionelle Gruppen waren mit den Reaktionsbedingungen kompatibel.

Don′t tell azole: The first metalcatalyzed direct coupling of metal sulfides with aryl halides and subsequent intramolecular condensation provided substituted benzothiazoles see scheme. A wide range of functional groups are tolerated under the reaction conditions.

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Intramolecular coupling of -keto 2-iodoanilides catalyzed by CuI/l-proline in DMSO occurs at room temperature, affording substituted 3-acyloxindoles in good yield. Electronic effects on the aromatic ring have little influence on this reaction. Variations at the 1, 3, 4, 5, and 6 positions of the oxindoles were achieved by employing the corresponding amides.

A novel total synthesis of apratoxin A is described, with key steps including the assembly of its ketide segment through a D‐proline‐catalyzed direct aldol reaction and Oppolzer's antialdol reaction and the preparation of its thiazoline unit in a biomimetic synthesis. An oxazoline analogue of apratoxin A has also been elaborated by a similar approach. This compound has a potency against HeLa cell proliferation only slightly lower than that of apratoxin A, whilst a C(40)‐demethylated oxazoline analogue of apratoxin A displays a much lower cytotoxicity and the C(37)‐epimer and C(37) demethylation product of this new analogue are inactive. These results suggest that the two methyl groups at C(37) and C(40) and the stereochemistry at C(37) are essential for the potent cellular activity of the oxazoline analogue of apratoxin A. Further biological analysis revealed that both synthetic apratoxin A and its oxazoline analogue inhibited cell proliferation by causing cell cycle arrest in the G1 phase.

Halipeptins A–D (1 a–d) are a family of natural cyclic depsipeptides isolated from marine sponges. Total syntheses of these four compounds are detailed in this report. The key elements in this synthesis include the elaboration of the polysubstituted decanoic acid parts by two asymmetric aldol reactions, assembly of the N‐methyl‐δ‐hydroxyisoleucine residue by using either aza‐Claisen rearrangement or methylation of aspartates as the key steps, and macrocyclization at the polysubstituted decanoic acid alanine site.

A short route for assembling clavepictines A and B and pictamine is described, which features elaboration of its trisubstituted piperidine moiety via condensation of a -keto sulfone with an l-alanine-derived bromide and subsequent alkylative cyclization and construction of its quinolizidine skeleton via a diastereoselective intramolecular conjugate addition. The possible stereochemical course for this conjugate addition is discussed.