Jiashan Li

Asymmetric alkylation is one of the most important methods for synthesizing chiral unnatural α-substituted α-amino acids. Herein, We reported an asymmetric alkylation of tert-butyl glycinate Schiff base catalyzed by copper/(4S,2R)-tBu-Phosferrox catalysts. This catalyst shows high catalytic performance in the asymmetric alkylation at 1 mol % catalyst loading, giving the products with up to 95% yield and >99% ee. This method was successfully applied to synthesize a series of phallotoxins chiral unnatural α-substituted α-amino acids and the key intermediate, such as α-AAs-7 (4,5-OH-Leu) derivatives.

Intelligent stimulus-triggered release and high drug-loading capacity are crucial requirements for drug delivery systems in cancer treatment. Based on the excessive intracellular GSH expression and pH conditions in tumor cells, a novel glutathione (GSH) and pH dual-responsive hydrogel was designed and synthesized by conjugates of glutamic acid-cysteine dendrimer with alginate (Glu-Cys-SA) through click reaction, and then cross-linked with polyethylene glycol (PEG) through hydrogen bonds to form a 3D-net structure. The hydrogel, self-assembled by the inner disulfide bonds of the dendrimer, is designed to respond to the GSH heterogeneity in tumors, with a remarkably high drug loading capacity. The Dox-loaded Glu-Cys-SA hydrogel showed controlled drug release behavior, significantly with a release rate of over 76% in response to GSH. The cytotoxicity investigation indicated that the prepared DOX-loaded hydrogel exhibited comparable anti-tumor activity against HepG-2 cells with positive control. These biocompatible hydrogels are expected to be well-designed GSH and pH dual-sensitive conjugates or polymers for efficient anticancer drug delivery.