Asian Journal of Organic Chemistry最新文献

A [4+2] annulation reaction between 1,2,3-thiadiazoles and para-quinone methides has been achieved. Various functionalized thiocoumarins are successfully obtained in up to 96% yield. The synthetic utility of this protocol is demonstrated by the 30 mmol scale reaction.

A novel Boc₂O-promoted cascade transformation has been developed for the efficient one-step synthesis of C5 sulfur-substituted oxazolidin-2-ones from thioepoxy amines. This method enables simultaneous oxazolidinone ring construction and side-chain sulfur incorporation via intramolecular cyclization, significantly improving synthetic step economy. Mechanistic studies, including NMR and x-ray analysis, suggest a 5-exo-tet cyclization pathway consistent with Baldwin's rules. This strategy expands the synthetic utility of oxazolidinone scaffolds, offering access to medicinally relevant sulfur-containing analogues with potential pharmacological applications.

Sclareol is well-documented for its potent anti-inflammatory properties, making it a promising candidate for chronic inflammatory disorders; however, it is toxic to normal cells. In order to address this, we have successfully synthesized a new series of arylated derivatives of sclareol via the Heck reaction. Among all the synthesized compounds, SCL-1 showed 92.81% viability at 20 uM, which is far better than the parent molecule. Further, synthesized compounds were evaluated for the first time for their anti-inflammatory potential. Based on cell viability assays, SCL-1 was further investigated in a lipopolysaccharide (LPS)-induced nitric oxide (NO) release assay in RAW 264.7 macrophages. Here, SCL-1 exhibited 38.39% inhibition, better than the parent molecule sclareol, which demonstrated 26.44% inhibition at 5 µM. These results suggest that SCL-1 exerts superior NO suppressive activity compared to the parent molecule. Given its significant NO inhibitory effect, SCL-1 was further assessed for its impact on pro-inflammatory cytokines. At a concentration of 20 µM, SCL-1 significantly inhibited TNF-α and IL-6 by 52.32% and 53.58%, respectively. Moreover, SCL-1 effectively mitigated LPS-induced oxidative stress, reducing reactive oxygen species (ROS) production by 47.69% at the same concentration. In silico and Swiss-ADMET studies of SCL-1 showed significant potential as a lead for the development of novel anti-inflammatory agents.

Breast cancer remains a significant global health concern, highlighting the need for the development of new therapeutic strategies. This study presents the design and synthesis of a novel series of chiral thiazoles (8a–8i) using an efficient synthetic route, achieving good yields (75%–98%). These compounds are explored as potential inhibitors targeting AKT1, a crucial player in the progression of breast cancer. The synthesized compounds were thoroughly characterized using high-resolution mass spectrometry and nuclear magnetic resonance (HRMS and NMR) spectroscopy. A comprehensive network pharmacology approach was employed to investigate potential target genes for the thiazoles (8a–8i) in breast cancer. This analysis successfully identified AKT1 as a crucial target for these compounds. The AKT1 gene plays a significant role in the growth and proliferation of cancer cells. Therefore, one objective of this study is to inhibit AKT1 using the newly prepared (8a–8i) to prevent cancer cell growth and ultimately induce their death. The thiazoles (8a–8i) were screened for ADMET properties and molecularly docked against the AKT1 target. Molecular dynamics simulations (RMSD and RMSF values) were conducted for the two lead compounds over 100 ns to assess their stability. All designed compounds exhibited favorable physicochemical and ADMET properties. Among them, (8b, 8d) were identified as novel lead molecules targeting AKT1.

A mild photoredox-catalyzed method for the C─N bond cleavage of aliphatic tertiary amines to construct medicinally significant α-ketoamides has been reported. The reaction showcases the simultaneous formation of C─N and C─O bonds in a single step. In this study, the tertiary amine acts as a dual-function reagent, serving both as a reductant and nitrogen source, thereby obviating the need for external nitrogen-based coupling partners in the presence of phenylacetylene and catalytic thiophenol. Beyond providing an easier route to complex molecules from simple starting materials, our work highlights the hidden utility of tertiary amines in photoredox catalysis, offering a platform for late-stage functionalization and C─N bond activation.