Synthesis and application of phosphorylated saccharides in researching carbohydrate-based drugs

• Published in: Bioorganic & medicinal chemistry 2022-08, Vol.68, p.116806-116806, Article 116806
• Main Authors: Wang, Ning, Kong, Yuanfang, Li, Jieming, Hu, Yulong, Li, Xiaofei, Jiang, Shiqing, Dong, Chunhong
• Format: Article
• Language: English
• Subjects: Biological activity; Phosphorylated saccharides; Structural modification; Structure-activity relationship; Synthesis
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2022.116806

[Display omitted] Phosphorylated saccharides are valuable targets in glycochemistry and glycobiology, which play an important role in various physiological and pathological processes. The current research on phosphorylated saccharides primarily focuses on small molecule inhibitors, glycoconjugate vaccines and novel anti-tumour targeted drug carrier materials. It can maximise the pharmacological effects and reduce the toxicity risk caused by nonspecific off-target reactions of drug molecules. However, the number and types of natural phosphorylated saccharides are limited, and the complexity and heterogeneity of their structures after extraction and separation seriously restrict their applications in pharmaceutical development. The increasing demands for the research on these molecules have extensively promoted the development of carbohydrate synthesis. Numerous innovative synthetic methodologies have been reported regarding the continuous expansion of the potential building blocks, catalysts, and phosphorylation reagents. This review summarizes the latest methods for enzymatic and chemical synthesis of phosphorylated saccharides, emphasizing their breakthroughs in yield, reactivity, regioselectivity, and application scope. Additionally, the anti-bacterial, anti-tumour, immunoregulatory and other biological activities of some phosphorylated saccharides and their applications were also reviewed. Their structure–activity relationship and mechanism of action were discussed and the key phosphorylation characteristics, sites and extents responsible for observed biological activities were emphasised. This paper will provide a reference for the application of phosphorylated saccharide in the research of carbohydrate-based drugs in the future.