Events & News

Events & News

Skeletal editing of pyrrolidines by nitrogen-atom insertion

Single-atom skeletal editing has emerged as a transformative strategy for modifying molecular frameworks—particularly cyclic scaffolds—by enabling precise, atom-level modifications without requiring de novo synthesis. N-heterocycles are privileged scaffolds in medicinal chemistry, playing critical roles in molecular recognition, pharmacokinetics, and physicochemical properties. Notably, 82% of FDA-approved small-molecule drugs (2013–2023) incorporate N-heterocycles, with pyridine, piperidine, pyrrolidine, and piperazine among the most prevalent. Despite their importance, methods for direct skeletal editing of saturated N-heterocycles (e.g., pyrrolidines) lag behind those for aromatic systems, due to challenges in cleaving and reforming inert C–N/C–C σ bonds without π-system activation.

2025-08-06

Gasdermin-Mediated Pyroptosis: At the Crossroads of Inflammation, Immunity, and Cancer Research

Pyroptosis is a programmed cell death mechanism characterized by cellular swelling, plasma membrane rupture, and the release of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). This cell death modality was initially discovered in macrophages combating pathogenic invasion. When cells detect pathogen intrusion, a family of proteins called Gasdermin (GSDM) becomes activated, forming pores in the cell membrane that lead to cellular rupture and death. This process not only eliminates infected cells but also recruits additional immune cells through the release of inflammatory signals, thereby enhancing the immune response.

2025-07-29

Atom Replacement Strategy Achieves Precise Regiocontrol in Pyrazole Alkylation

Selectivity represents one of the fundamental principles in organic synthesis. From a retrosynthetic perspective, the conventional approach to addressing selectivity challenges involves identifying the determinant bonds and subsequently attempting to control their formation. While this strategy has provided synthetic solutions across numerous domains, it proves inadequate for many significant reactions, necessitating the development of innovative approaches to address these persistent challenges.

2025-07-28

3-Selective Pyridine Halogenation via Zincke Imine Intermediates

Halogenation of pyridines is of critical importance in the development of pharmaceuticals and agrochemicals, as the introduction of halogen atoms can enable a wide range of subsequent bond-forming transformations. However, achieving selective halogenation at the 3-position of pyridine remains a significant challenge. Existing methods often suffer from harsh reaction conditions, require directing groups, or exhibit poor compatibility with functional groups.

2025-07-21

Cost-effective and High-Performance Ionizable Lipids for mRNA-LNP Vaccines: One-Pot Ugi-4CR Strategy and Preclinical Evaluation

The COVID-19 pandemic underscored the enormous potential of mRNA vaccine technology for infectious disease prevention. mRNA vaccines require efficient delivery vehicles—typically lipid nanoparticles (LNPs)—to enable translation of antigenic proteins and induction of humoral and cellular immunity. Ionizable lipids (ILs) are the pivotal component in LNPs, critically influencing mRNA encapsulation, endosomal escape, biodistribution, and overall vaccine efficacy. However, most commercial ILs are produced via multi-step organic syntheses, resulting in elevated costs and quality control challenges. The development of a simplified, cost-effective, and robust synthetic approach to ILs is crucial for the large-scale, global deployment of mRNA vaccine technologies.

2025-07-16

Optimizing Hydroxyl Groups: The Tertiary Alcohol Advantage in Medicinal Chemistry

Previous research has established that the strategic substitution of a hydrogen atom with a hydroxyl group (H-to-OH) effectively diminishes molecular lipophilicity, enhances aqueous solubility, and attenuates hERG inhibition. Notwithstanding these advantageous properties, hydroxyl groups (OH) are not universally preferred in pharmaceutical design. This selectivity arises because in primary and secondary alcohols, the OH moiety constitutes a metabolic vulnerability, susceptible to oxidative processes and glucuronidation reactions. Furthermore, hydroxyl groups may adversely affect cell membrane permeability parameters. Conversely, tertiary alcohols (3° ROH) frequently demonstrate superior metabolic profiles. This enhancement stems from the structural configuration of 3° ROH, where oxidation at the carbon-hydroxyl junction is sterically hindered, and adjacent alkyl substituents provide protective steric effects to the OH group, thereby reducing susceptibility to glucuronidation and mitigating permeability constraints.

2025-07-15

Modular Arene Functionalization by Differential 1,2-Diborylation

A nickel-catalyzed vicinal diborylation method that 12 can directly install two chemically differentiated boryl groups in a regio- and site-selective manner using readily 13 available aryl triflates or chlorides as substrates. This reaction operates under mild reaction conditions and shows a broad substrate scope and excellent functional group tolerance. Each boryl group can be independently transformed into various groups, providing an efficient modular, regioselective, and divergent approach to access diverse vicinal difunctionalized arenes, showing promise for constructing analogue libraries.

2025-07-14

Copper-Catalyzed Enantioselective Three-Component Carboamidation of Styrenes with Alkanes and Amides

The efficient assembly of valuable chiral molecules from readily available and low-cost chemical feedstocks remains one of the most challenging tasks in synthetic chemistry today. Radical-mediated three-component carboamination of alkenes offers an attractive strategy for addressing this challenge. However, most existing reports focus on racemic examples and are largely limited to activated alkenes, preactivated alkylation reagents, or sufficiently active nucleophiles. Herein, the authors report a highly enantioselective three-component carboamidation of styrenes with unactivated alkanes and weakly nucleophilic amides. Enantioselective control is achieved by using chiral cationic copper catalysts. This method enables the synthesis of various optically active amides with excellent enantioselectivity. Mechanistic studies reveal that the reaction proceeds via hydrogen atom transfer from the alkane, followed by radical addition to the olefin.

2025-07-09

Novel Difluorocyclobutyl Derivatives as Potent Glucagon-Like Peptide-1 Receptor Agonists with Reduced hERG Inhibitory Activity

Research conducted at the College of Ocean, Zhejiang University, by Professor Wanjing Ding and Professor Zhongjun Ma has led to significant advances in pharmaceutical development.

2025-06-17

STAT3: A Critical Target in Cancer Research

In the frontier of cancer research, STAT3 emerges as a crucial signalling molecule expressed across various tissues, regulating genes associated with cancer cell growth, proliferation, angiogenesis, metastasis, drug resistance, and immune evasion. Its persistent activation is implicated in multiple oncogenic mechanisms, establishing it as a primary target in cancer research.

2025-05-29

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