A highly diastereoselective approach towards the synthesis of quaternary center-containing cyclopentenes was developed. The tandem Michael/aldol/rearrangement processes occurred under mild reaction conditions.

As an extremely popular natural product, berberine (BER) is mainly used for gastroenteritis and diarrhoea caused by bacteria. Research has also revealed the potent and extensive pharmacological properties of BER including its anti-arrhythmic, anti-tumour, anti-inflammatory and hypoglycemic activities and so on; therefore, BER is a promising drug for further development. However, its commercial form with hydrochloride exhibits poor stability and solubility, which are detrimental to its clinical therapeutic effects. For these purposes, the salt form was regulated via the reactive crystallization of 8-hydroxy-7,8-dihydroberberine (8H-HBER) with five pharmaceutically suitable organic acids including malonic acid (MA), L-tartaric acid (LTA), D-tartaric acid (DTA), DL-tartaric acid (DLTA) and citric acid (CA), resulting in the six novel solid forms 1BER-1LTA-1W, 1BER-1DTA-1W, 1BER-1DLTA and 2BER-2CA as well as two rare multi-stoichiometric solid forms 1BER-1MA and 1BER-2MA-2W. The preparation of the multi-stoichiometric products was greatly influenced by both the crystallization solvent type and the molar ratio of reactants. The structures of these multi-component solid forms were determined using single-crystal X-ray diffraction and further characterized by powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy. Stability experiments showed that all samples prepared had superior physical stability under high temperature and high humidity. Furthermore, dissolution experiments demonstrated that the maximum apparent solubilities (MAS) of all the products were significantly improved compared with the commercial form of BER in dilute hydrochloric solution (pH = 1.2). In particular, the MAS of 1BER-1MA in dilute hydrochloric solution is as high as 34 times that of the commercial form. In addition, it is preliminarily confirmed that the MAS of the samples prepared in pure water and dilute hydrochloric solution is primarily influenced by a combination of factors including the packing index, intermolecular interactions, affinity of the counter-ion to the solvent, the molar ratio of the drug to counter-ion in the product and the common ion effect. These novel solids are potential candidates for BER solid forms with improved oral dosage design and may prompt further development.

To develop new, more effective and lower toxicity antitumor dihydroartemisinin (DHA) nanocomplexes, a DHA prodrug synthesized in this study was used to prepare DHA prodrug self-assembled nanocomplexes (DHANPs) by molecular self-assembly technology. The optimization, pharmacokinetics and in vitro and in vivo antitumor efficiency of DHANPs were assessed. The results showed that the entrapment efficiency, drug loading, particle size and zeta potential of the optimized formulation were 92.37 ± 3.68%, 76.98 ± 3.07%, 145.9 ± 2.11 nm and −16.0 ± 0.52 mV, respectively. DHANPs had a uniform size distribution and good stability during storage. The release of DHA prodrugs from DHANPs was slow in a PBS solution (pH 7.4). The pharmacokinetic study indicated that DHANPs could significantly improve the blood concentration of DHA. DHANPs exhibited lower cytotoxicity to 4T1 cells. More importantly, DHANPs could increase the quality life of mice in comparison with that of the DHA solution in 4T1 tumor-bearing mice. In short, the optimized DHA prodrug nanocomplexes show good long-term stability during the experimental time, extend the life-cycle of DHA in rats and can act as a prospective nano-drug delivery system for future artemisinin-based anti-tumor drugs.

The first method for carrying out enantioselective, organocatalytic Michael-type Friedel–Crafts alkylation of naphthol and unsaturated pyrazolones was reported.