Application of β-Keto Acylpyrazoles as 2C Synthons in Asymmetric Cyclizations of -Hydroxychalcones: Stereoselective Construction of -3,4-Dihydrocoumarins.

An asymmetric tandem esterification/Michael addition reaction of β-keto acylpyrazoles with -hydroxychalcones has been established under the catalysis of a bifunctional squaramide-tertiary amine. A wide variety of biorelevant 3,4-dihydrocoumarin derivatives were generally obtained in high yields (up to 93%) with excellent diastereo- and enantioselectivities (>19:1 dr, up to 93% ee) under mild reaction conditions. This reaction represents the successful application of β-keto acylpyrazoles as 2C building blocks in catalytic asymmetric cyclizations.

Discovery of new pesticide candidates from nature: design, synthesis and bioactivity research of rutaecarpine derivatives.

Background: The invasion of viruses and fungi can cause pathological changes in the normal growth of plants and is an important factor in causing plant infectious diseases. These pathogenic microorganisms can also secrete toxic metabolites, affecting crop quality and posing a threat to human health. In this work, we selected the natural product rutaecarpine as the lead compound to achieve the total synthesis and structural derivation.

Synthesis, structural modification, and biological activity of a novel bisindole alkaloid iheyamine A.

Diseases caused by plant viruses and pathogens pose a serious threat to crop yield and quality. Traditional pesticides have gradually developed drug resistance and brought certain environmental safety issues during long-term overuse. There is an urgent need to discover new candidate compounds to address these issues.

Photoredox Nickel-Catalysed Stille Cross-Coupling Reactions.

The Stille cross-coupling reaction is one of the most common strategies for the construction of C-C bonds. Despite notable strides in the advancement of the Stille reaction, persistent challenges persist in hindering its greener evolution. These challenges encompass multiple facets, such as the high cost of precious metals and ligands, the demand for various additives, and the slow reaction rate.

Stereoselective alkyl -glycosylation of glycosyl esters anomeric C-O bond homolysis: efficient access to -glycosyl amino acids and -glycosyl peptides.

-Glycosyl peptides possess excellent metabolic stability and therapeutic properties and thus play critical roles in biological studies as well as drug discoveries. However, the limited accessibility of -glycosyl amino acids has significantly hindered the broader research of their structural features and mode of action. Herein, for the first time we disclose a novel visible-light-driven radical conjugate addition of 1,4-dihydropyridine (DHP)-derived glycosyl esters with dehydroalanine derivatives, generating -glycosyl amino acids and -glycosyl peptides in good yields with excellent stereoselectivities.

Self-supervised learning enables 3D digital subtraction angiography reconstruction from ultra-sparse 2D projection views: A multicenter study.

3D digital subtraction angiography (DSA) reconstruction from rotational 2D projection X-ray angiography is an important basis for diagnosis and treatment of intracranial aneurysms (IAs). The gold standard requires approximately 133 different projection views for 3D reconstruction. A method to significantly reduce the radiation dosage while ensuring the reconstruction quality is yet to be developed.

Iodine-mediated electrochemical C(sp)-H cyclization: the synthesis of quinazolinone-fused N-heterocycles.

An efficient iodine-mediated electrochemical C(sp)-H cyclization was developed under mild conditions. A variety of functionalized quinazolinone-fused N-heterocycles can be obtained with good to excellent yields by virtue of this method. The reaction features a broad substrate scope and scalability, and is metal-free and chemical oxidant-free.

Electrosynthesis of Quinazolines and Quinazolinones via an Anodic Direct Oxidation C(sp)-H Amination/C-N Cleavage of Tertiary Amine in Aqueous Medium.

An electrochemical synthesis for quinazolines and quinazolinones was developed via a C(sp)-H amination/C-N cleavage by virtue of the anodic oxidation. The reaction can be carried out in aqueous media under mild conditions to afford the desired products with high yields. The reaction mechanism was proposed after detailed investigation.

Electrosynthesis of 2-(1,3,4-Oxadiazol-2-yl)aniline Derivatives with Isatins as Amino-Attached C1 Sources.

An intramolecular decarboxylative coupling reaction for the construction of 2-(1,3,4-oxadiazol-2-yl)aniline derivatives was developed from readily available isatins and hydrazides by virtue of electrochemistry. In this reaction, isatins were employed as amino-attached C1 sources, providing a variety of 2-(1,3,4-oxadiazol-2-yl)aniline derivatives with moderate to good yields.

Iodine-Mediated Electrochemical C(sp)-H Amination: Switchable Synthesis of Indolines and Indoles.

A metal-free electrochemical intramolecular C(sp)-H amination using iodine as a mediator was developed. This method enables a switchable synthesis of indoline and indole derivatives, respectively, from easily available 2-vinyl anilines.

3-Nitro-3,4-dihydrocoumarins: valuable precursors for the synthesis of enantiomerically enriched masked quaternary α-amino acid derivatives with a 3,4-dihydrocoumarin scaffold.

A bifunctional squaramide catalyzed enantioselective formal [2 + 4] annulation reaction with 3-nitro-3,4-dihydrocoumarins and ortho-quinone methide has been developed. Novel chiral masked quaternary α-amino acid derivatives with a 3,4-dihydrocoumarin scaffold are obtained in a highly stereocontrolled manner. Representative transformation of the annulation product to a biologically important quaternary α-amino acid derivative is achieved without any appreciable loss in the diastereo- and enantioselectivity.

Electrocatalytic Three-Component Reaction: Synthesis of Cyanide-Functionalization Imidazo-Fused -Heterocycles.

An electrochemical three-component cyclization was developed under metal-free conditions, which provides a novel and facile approach for the construction of cyanide-functionalization imidazo-fused -heterocycles. A variety of cyanide-functionalization imidazo-fused -heterocycles can be obtained from easily available methyl -heteroaromatics, primary alkylamines, and trimethylsilyl cyanide with good to excellent yields. The reaction features a broad scope of substrates, scalability, and mild conditions.

Application of Entropy Spectral Method for Streamflow Forecasting in Northwest China.

Streamflow forecasting is vital for reservoir operation, flood control, power generation, river ecological restoration, irrigation and navigation. Although monthly streamflow time series are statistic, they also exhibit seasonal and periodic patterns. Using maximum Burg entropy, maximum configurational entropy and minimum relative entropy, the forecasting models for monthly streamflow series were constructed for five hydrological stations in northwest China.

Electrocatalytic Tandem Synthesis of 1,3-Disubstituted Imidazo[1,5- a]quinolines via Sequential Dual Oxidative C(sp3)-H Amination in Aqueous Medium.

An NHI-mediated tandem electrosynthesis of 1,3-disubstituted imidazo[1,5- a]quinolines was developed from readily available starting materials in aqueous medium, affording a variety of 1,3-disubstituted imidazo[1,5- a]quinolines with good to excellent yields.

Electrocatalytic Intermolecular C(sp)-H/N-H Coupling of Methyl N-Heteroaromatics with Amines and Amino Acids: Access to Imidazo-Fused N-Heterocycles.

An efficient NHI-mediated intermolecular annulation of methyl N-heteroaromatics with amines/amino acids was developed by virtue of anodic oxidation, providing a variety of functionalized imidazo-fused N-heterocycles with good to excellent yields. The practicality of this protocol was demonstrated by the readily available starting materials, broad substrate scope, water tolerance, scalability, and the diverse transformations of the electrolysis product.

Asymmetric Formal [4 + 2] Annulation of o-Quinone Methides with β-Keto Acylpyrazoles: A General Approach to Optically Active trans-3,4-Dihydrocoumarins.

An asymmetric cascade reaction between β-keto acylpyrazoles and o-quinone methides in a formal [4 + 2] fashion to access potentially pharmacological active trans-3,4-dihydrocoumarins has been achieved efficiently by using a quinine-based chiral squaramide as the catalyst. The desired products were obtained in high yields with excellent diastereo- and enantioselectivities (up to 96% yield, >19/1 dr and 96% ee) under mild reaction conditions.

Autologous Bone Marrow-Derived Stem Cells for Treating Diabetic Neuropathy in Metabolic Syndrome.

Diabetic neuropathy is one of the most common and serious complications of diabetes mellitus and metabolic syndrome. The current therapy strategies, including glucose control and pain management, are not effective for most patients. Growing evidence suggests that infiltration of inflammation factors and deficiency of local neurotrophic and angiogenic factors contribute significantly to the pathologies of diabetic neuropathy.

Chemical Synthesis of K34-Ubiquitylated H2B for Nucleosome Reconstitution and Single-Particle Cryo-Electron Microscopy Structural Analysis.

Post-translational modifications (e.g., ubiquitylation) of histones play important roles in dynamic regulation of chromatin.

Organocatalyzed Asymmetric Michael Addition of 1-Acetylindolin-3-ones to β,γ-Unsaturated α-Ketoesters: An Access to Chiral Indolin-3-ones with Two Adjacent Tertiary Stereogenic Centers.

Asymmetric Michael addition of 1-acetylindolin-3-ones to β,γ-unsaturated α-ketoesters was investigated for the synthesis of chiral indolin-3-ones with two adjacent tertiary stereogenic centers. Under the catalysis of a chiral bifunctional squaramide derived from l-tert-leucine, a wide range of 1-acetylindolin-3-ones and β,γ-unsaturated α-ketoesters were well-tolerated in this transformation to provide the corresponding novel densely functionalized chiral indolin-3-one derivatives in high yield with excellent diastereo- and enantioselectivity under mild reaction conditions.

Stereocontrolled Construction of Tetrahydropyrano[2,3-c]pyrazole Scaffold via an Organocatalyzed Formal [3 + 3] Annulation.

A bifunctional squaramide catalyzed enantioselective formal [3 + 3] annulation reaction with pyrazolin-5-ones and nitroallylic acetates has been developed. Densely substituted tetrahydropyrano[2,3-c]pyrazoles with two adjacent stereogenic centers are obtained in a highly stereocontrolled manner. Representative transformation of the annulation product to a biologically important fused dihydroisoquinoline is achieved without any appreciable loss in the diastereo- and enantioselectivity.

Application of "Hydrogen-Bonding Interaction" in Drug Design. Part 2: Design, Synthesis, and Structure-Activity Relationships of Thiophosphoramide Derivatives as Novel Antiviral and Antifungal Agents.

On the basis of the structure of natural product harmine, lead compound 18, and the structure of compounds in part 1, a series of thiophosphoramide derivatives 1-17 were designed and synthesized from various amines in one step. Their antiviral and antifungal activities were evaluated. Most of the compounds showed significantly higher antiviral activity against tobacco mosaic virus (TMV) than commercial virucide ribavirin.

Organocatalytic multicomponent synthesis of polysubstituted pyrroles from 1,2-diones, aldehydes and arylamines.

We have developed an organocatalyzed three-component reaction of 1,2-diones, aldehydes and arylamines, which provides an efficient approach to access polysubstituted pyrroles. In the catalysis of 4-methylbenzenesulfonic acid monohydrate, the reactions of a wide range of 1,2-diones, arylamines and aldehydes took place smoothly to generate the corresponding polysubstituted pyrroles in acceptable to good yields under mild reaction conditions.

Application of "hydrogen bonding interaction" in new drug development: design, synthesis, antiviral activity, and SARs of thiourea derivatives.

A series of simple thiourea derivatives were designed based on the structure of natural product harmine and lead compound and synthesized from amines in one step. The antiviral activity of these thiourea derivatives was evaluated. Most of them exhibited significantly higher anti-TMV activity than commercial plant virucides ribavirin, harmine, and lead compound.

Stereoselective synthesis of highly functionalized nitrocyclopropanes through the organocatalyic Michael-addition-initiated cyclization of bromonitromethane and β,γ-unsaturated α-ketoesters.

A highly diastereo- and enantioselective cyclopropanation of β,γ-unsaturated α-ketoesters with bromonitromethane has been successfully developed through a domino Michael-addition/intramolecular-alkylation strategy. Acceptable yields (up to 89%) and enantioselectivities (up to 96% ee) have been obtained.