N-heterocyclic carbene catalyzed [2 + 3] annulation reaction for the synthesis of trifluoroethyl 3,2'-spirooxindole γ-lactam.

Asymmetric catalytic processes promoted by N-heterocyclic carbenes (NHCs) hold great potential for the sustainable preparation of chiral molecules. However, catalyzing the reactions by manipulating the reactive intermediates is challenging. We report herein that the known NHC-catalyzed [3 + 2] annulation reaction between ketimine and enal can also be turned into a [2 + 3] annulation reaction for the highly enantioselective direct synthesis of trifluoroethyl 3,2'-spirooxindole γ-lactams (4) through timely catalysis of the intermediates. DFT calculations revealed that this transformation included the key step of the nucleophilic attack of the Breslow intermediate M2 derived from NHC and enal (2) to the unattacked ketimine (1). Our study demonstrates that it is possible to tune the desired selectivities through the dynamic catalysts of the reactive intermediates.

Hierarchical Bamboo/Silver Nanoparticle Composites for Sustainable Water Purification.

Water reclamation is the most effective way to continuously provide clean water to combat catastrophic global water scarcity. However, current technology for water purification is not conducive to sustainability due to the high energy consumption and negative environmental impact. Here, we introduce an innovative method by utilizing the hierarchical microstructure of bamboo for water purification. Natural bamboo was delignified followed by freeze-drying to obtain a bamboo aerogel with a porosity of 72.0%; then, the bamboo aerogel was coated with silver nanoparticles to form a hierarchical bamboo/silver nanoparticle composite. The scanning electron microscopy images and energy-dispersive X-ray spectroscopy results indicated that the silver nanoparticles were uniformly attached to the parenchyma cell surface. By physical adsorption and catalytic reduction, the bamboo/silver nanoparticle composite was able to degrade methylene blue by more than 96.7%, which is mainly attributed to the large specific surface area of the bamboo providing more space for the purification reaction. This composite can be potentially used for board applications with its high porosity, mechanical reliability, and sustainability.

A close look into the biological and synthetic aspects of fused pyrazole derivatives.

The fusion of pyrazole scaffold with other skeletons creates a class of attractive molecules, demonstrating significant biological and chemical potentiality in the development of medicinal chemistry. Over the past few decades, numerous biologically active molecules featuring fused pyrazole moieties have been excavated and synthesized, some of which represented by sildenafil have been marketed as drugs, and the biological importance together with chemical synthesis strategies of fused pyrazole compounds, including structural modification based on lead compounds, have been steadily progressing. In this review, we focused our attention on the biological importance of fused pyrazoles and highlighted recent progress in the synthesis of this framework over the past 10 years. What' s more, the limitations, challenges, and future prospects were proposed, wishing to provide references for the development of pyrazole fused frameworks in the field of medicinal chemistry. Contents.

Voacamine is a novel inhibitor of EGFR exerting oncogenic activity against colorectal cancer through the mitochondrial pathway.

Colorectal cancer (CRC), among the most aggressive and prevailing neoplasms, is primarily treated with chemotherapy. Voacamine (VOA), a novel bisindole natural product, possesses a variety of conspicuous pharmacological activities. Within the current research, we evaluated in vitro and in vivo the anticancer efficacy of VOA against CRC and its potential mechanisms. Our results illustrated that VOA concentrationdependently suppressed the proliferation and migration of CT26 and HCT116 cells as correspondingly indicated by IC50 values of 1.38 ± 0.09 µM and 4.10 ± 0.14 µM. Furthermore, treatment of VOA also suppressed tumor cell colony formation, escalated the late-stage apoptosis rate of tumor cells, and evoked cell cycle of CT26 and HCT116 cells arrest inhibition in G2-M and G0-G1 phases, respectively. Meanwhile, VOA markedly disrupted the mitochondrial membrane potential eliciting mitochondrial dysfunction, decreased ATP production, and intermediated an enhanced accumulation of intracellular reactive oxygen species with a concentration-dependent pattern, accompanied by elevated expression levels of pro-apoptotic related protein Bax, Cyt-C, cleaved caspases 3/8/9 and by diminished Bcl-2, Bid, PRAP and caspases 3/8/9 expression. Further mechanistic studies revealed VOA treatment suppressed the EGFR/PI3K/Akt pathway with the evidence of the decreased phosphorylation proteins of EGFR, PI3K, Akt, and downstream proteins of p-mTOR, p-NF-kB, and p-P70S6. Additionally, molecular dynamics simulations further displayed VOA could enter the EGFR pocket followed by multiple mutual interaction effects. Interestingly, the EGFR activator (NSC228155) could slack the inhibitory capability of VOA on the EGFR/PI3K/Akt pathway as well as VOA-induced impairment of mitochondrial function. Finally, administration of VOA (15, 30 mg/kg every 2 days, i.p., for 16 days) in CT26 syngeneic mice dose-dependently suppressed the neoplastic development without appreciable organ toxicities. Taken together, our study demonstrated that VOA may be a prospective therapeutic agent for the treatment of CRC.

Construction of multi-substituted pyrazoles via potassium carbonate-mediated [3 + 2] cycloaddition of in situ generated nitrile imines with cinnamic aldehydes.

A highly efficient potassium carbonate-mediated [3 + 2] cycloaddition reaction of hydrazonoyl chlorides with cinnamic aldehydes to furnish multi-substituted pyrazoles under nontoxic and mild conditions has been developed. A plausible stepwise cycloaddition reaction mechanism is proposed. This protocol featured broad substrate coverage, good functional group tolerance, wide scalability, and operational simplicity, as well as conveniently constructed pyrazole scaffolds.