Synthesis and glycosidase inhibition evaluation of (3S,4S)-3-((R)-1,2-dihydroxyethyl)pyrrolidine-3,4-diol

• Published in: Carbohydrate research 2016-11, Vol.434, p.33-36
• Main Authors: Zhang, En, Bai, Peng-Yan, Sun, Wei, Wang, Shang, Wang, Ming-Ming, Xu, Shuai-Min, Liu, Hong-Min
• Format: Article
• Language: English
• Subjects: Azasugar; Cyclization; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Glycoside Hydrolases - antagonists & inhibitors; Imino Sugars - chemical synthesis; Imino Sugars - chemistry; Imino Sugars - pharmacology; Isomer; Molecular Structure; One-pot reaction; Pyrrolidines - chemical synthesis; Pyrrolidines - chemistry; Pyrrolidines - pharmacology; Reductive cyclization; Stereoisomerism
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2016.08.003

A new azasugar (3S,4S)-3-((R)-1,2-dihydroxyethyl)pyrrolidine-3,4-diol (1) was obtained from commercially available d-glucose using one-pot reductive cyclization as a key step. The target product, i.e., the iminosugar isomer, was obtained in 10 steps and 24.3% overall yield. Only three column chromatography purifications were needed in this synthesis. The biological activity of the target molecule as glycosidase inhibitor was studied, but the inhibitory activity against four glycosidases was not good (IC50 > 100 μM). A new azasugar isomer (3S,4S)-3-((R)-1,2-dihydroxyethyl)pyrrolidine-3,4-diol was obtained from D-glucose in ten steps and 24.3% overall yield using one-pot reduction cyclization as the key step. Only three column chromatography purifications were needed in this synthesis. Biological activity evaluation as inhibitor against glycosidase were studied but the results were not ideal. [Display omitted] •A new azasugar was synthesized using one-pot reaction as a key step.•Our method plays an important role in the research of new azasugars.•The glycosidase inhibitory activity of the target molecule were not ideal.