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Zamoner, Luís Otávio B., Aragão-Leoneti, Valquíria, Mantoani, Susimaire P., Rugen, Michael D., Nepogodiev, Sergey A., Field, Robert A. 
ORCID: https://orcid.org/0000-0001-8574-0275 and Carvalho, Ivone
(2016)
CuAAC click chemistry with N-propargyl 1,5-dideoxy-1,5-imino-D-gulitol and N-propargyl 1,6-dideoxy-1,6-imino-D-mannitol provides access to triazole-linked piperidine and azepane pseudo-disaccharide iminosugars displaying glycosidase inhibitory properties.
Carbohydrate Research, 429.
pp. 29-37.
ISSN 0008-6215
Abstract
Protecting group-free synthesis of 1,2:5,6-di-anhydro-D-mannitol, followed by ring opening with propargylamine and subsequent ring closure produced a separable mix of piperidine N-propargyl 1,5-dideoxy-1,5-imino-D-gulitol and azepane N-propargyl 1,6-dideoxy-1,6-imino-D-mannitol. In O-acetylated form, these two building blocks were subjected to CuAAC click chemistry with a panel of three differently azide-substituted glucose building blocks, producing iminosugar pseudo-disaccharides in good yield. The overall panel of eight compounds, plus 1-deoxynojirimycin (DNJ) as a benchmark, was evaluated as prospective inhibitors of almond β-glucosidase, yeast α-glucosidase and barley β-amylase. The iminosugar pseudo-disaccharides showed no inhibitory activity against almond β-glucosidase, while the parent N-propargyl 1,5-dideoxy-1,5-imino-D-gulitol and N-propargyl 1,6-dideoxy-1,6-imino-D-mannitol likewise proved to be inactive against yeast α-glucosidase. Inhibitory activity could be reinstated in the former series by appropriate substitution on nitrogen. The greater activity of the piperidine could be rationalized based on docking studies. Further, potent inhibition of β-amylase was observed with compounds from both the piperidine and azepane series.
| Item Type: | Article |
|---|---|
| Additional Information: | Publisher Copyright: © 2016 Elsevier Ltd. All rights reserved. |
| Uncontrolled Keywords: | click chemistry,cuaac reaction,glycosidase inhibition,pseudo-disaccharide iminosugars,analytical chemistry,biochemistry,organic chemistry ,/dk/atira/pure/subjectarea/asjc/1600/1602 |
| Faculty \ School: | Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 04 Sep 2024 13:34 |
| Last Modified: | 04 Nov 2024 13:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96525 |
| DOI: | 10.1016/j.carres.2016.04.020 |
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