The Optimization of the Synthesis Process and the Identification of Levobupivacaine Hydrochloride.

In this study, we not only optimized and improved the synthesis process of levobupivacaine hydrochloride (21) but also conducted a comprehensive exploration of critical industrial-scale production details, and a novel high-performance liquid chromatography (HPLC) analysis method was developed. Starting with the readily available and cost-effective (R,S)-N-(2,6-dimethylphenyl)piperidine-2-carboxamide (28) as the initial material and utilizing l-(-)-dibenzoyl tartaric acid (29) for chiral separation, and then through substitution and a salting reaction, levobupivacaine hydrochloride (21) was obtained with high purity (chemical purity of 99.90% and enantiomeric excess (ee) values of 99.30%). The total yield of the three steps was 45%. Structures of intermediates and the final product were confirmed using nuclear magnetic resonance (NMR) (1H NMR, 13C NMR), mass spectrometry (MS), and elemental analysis. The crystal structure of the final product was determined through differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). Furthermore, we evaluated the risk of the substitution reaction using a reaction calorimeter and accelerating rate calorimetry (ARC). This process offers the advantages of simple operation, greenness, safety, controllable quality, and cost-effectiveness. It provides reliable technical support for the industrial-scale production of levobupivacaine hydrochloride (21), which is of significant importance in meeting clinical demands. Pilot-scale production has already been successfully completed by China National Medicines Guorui Pharmaceutical Co., Ltd., with a production scale of 20 kg.

Targeting Periplakin of Novel Benzenesulfonamides as Highly Selective Agonists for the Treatment of Vitiligo.

Vitiligo is the most common cause of depigmentation worldwide, with immunosuppressive treatments often being inefficient and prone to recurrence, making it essential to identify new therapeutic targets. Periplakin (PPL) has been identified and confirmed as a key factor in vitiligo-related depigmentation. Based on this, a series of selective PPL agonists, specifically benzenesulfonamides, have been developed. Among these, compound I-3 exhibits superior efficacy compared to ruxolitinib, the only FDA-approved treatment for vitiligo. I-3 has been shown to increase cAMP levels by regulating PPL, which enhances MITF expression, a key transcription factor in melanin biosynthesis. Additionally, I-3 promotes melanin production by regulating tryptophan metabolism. In summary, PPL is a promising drug target, and I-3 has strong potential for future treatment of vitiligo due to its high selectivity and favorable druggability.

A squaraine-based fluorescence turn on chemosensor with ICT character for highly selective and sensitive detection of Al3+ in aqueous media and its application in living cell imaging.

A novel and simple squaraine-based fluorescent chemosensor SQ-BH bearing the benzoylhydrazine moiety was developed for the highly sensitive and selective detection of Al3+ in methanol-water mixture. The chemosensing behaviors of SQ-BH and its binding interaction with Al3+ were explored by various spectroscopic analyses. The reversibility of Al3+ recognition process was investigated using EDTA. The results of experiments and DFT/TDDFT calculations revealed that the chemosensor SQ-BH obeyed a turn on mechanism which was associated with the inhibited photoinduced electron transfer (PET), the enhanced intramolecular charge transfer (ICT) and the activated chelation enhanced fluorescence (CHEF). Furthermore, the fluorescent chemosensor SQ-BH whose excellent biocompatibility was confirmed by a standard MTT assay could be used to detect Al3+ in living cells, indicating its potential application value in biological fields.