An Efficient Strategy for the Chemo‐Enzymatic Synthesis of Bufalin Glycosides with Improved Water Solubility and Inhibition against Na+, K+‐ATPase

• Published in: Chemistry & biodiversity 2020-11, Vol.17 (11), p.e2000529-n/a
• Main Authors: Liu, Yan, Xu, Wei, Huang, Zhao‐He, Guo, Jun, Jiang, Ren‐Wang
• Format: Article
• Language: English
• Subjects: Bufalin; Catalysis; Chemical synthesis; Enzymatic synthesis; Glycosides; Glycosylation; High-performance liquid chromatography; Liquid chromatography; Na+, K+-ATPase; Na+/K+-exchanging ATPase; Solubility; Strategy; water solubility
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.202000529

In this study, bufalin was glycosylated by an efficient chemo‐enzymatic strategy. Firstly, 2‐chloro‐4‐nitrophenyl‐1‐O‐β‐D‐glucoside (sugar donors) was obtained by chemical synthesis. Then, the glycosylation of the bufalin was achieved with the synthesized sugar donor under the catalysis of two glycosyltransferases (Loki and ASP). Finally, two glycosides, i. e., bufalin‐3‐O‐β‐D‐glucopyranoside and bufalin‐3‐O‐[β‐D‐glucopyranosyl‐(1→2)‐β‐D‐glucopyranoside)], were obtained by preparative HPLC. Compared to our previously reported sole chemical (total yield 10 % in four steps) or enzymatic methods (30 %), our combined chemo‐enzymatic strategy in this article greatly improves the yields of monoglycoside (68 %) and diglycoside (21 %) and decreased the experimental cost (90 %). Furthermore, we tested the water solubility of these glycosides and found that the water solubilities of the two glycosides were 13.1 and 53.7 times of bufalin, respectively. In addition, the inhibitory activity of these glycosides against Na+, K+‐ATPase were evaluated. The mono‐glycosylated compound showed more potent activity than bufalin, while the diglycosylated compound was less potent.