Back to Search
Start Over
Synthesis and glycosidase inhibition of 3,4,5-trihydroxypiperidines using a one-pot amination-cyclisation cascade reaction.
- Source :
-
Carbohydrate research [Carbohydr Res] 2024 Sep; Vol. 543, pp. 109198. Date of Electronic Publication: 2024 Jun 27. - Publication Year :
- 2024
-
Abstract
- Trihydroxypiperidines are a therapeutically valuable class of iminosugar. We applied a one-pot amination-cyclisation cascade reaction to synthesise 3,4,5-trihydroxypiperidine stereoisomers in three steps from commercially available pentoses and in excellent overall yields. Using our methodology, the yields of the syntheses of meso-1, meso-2 and 3L are the highest reported to date. The synthetic methodology was readily extended to the three-step synthesis of N-alkyl derivatives by replacing the ammonia nitrogen source with a primary amine. The trihydroxypiperidines and N-alkyl analogues were screened for enzyme inhibitory activity using Fabrazyme (Fabry disease), GCase (Gaucher's disease), Agrobacterium sp. β-glucosidase, and Escherichia coli β-galactosidase. N-Phenylethyl 3,4,5-trihydroxypiperidine (N-phenylethyl-1-(3R,4R,5S)-piperidine-3,4,5-triol) showed good inhibitory activity of Fabrazyme (K <subscript>i</subscript>  = 46 μM). This activity was abolished when the N-phenylethyl group was removed or replaced with a non-aromatic alkyl chain.<br />Competing Interests: Declaration of competing interest The authors y declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Amination
Cyclization
Glycoside Hydrolases antagonists & inhibitors
Glycoside Hydrolases metabolism
Escherichia coli drug effects
Escherichia coli enzymology
Molecular Structure
Piperidines chemistry
Piperidines pharmacology
Piperidines chemical synthesis
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors pharmacology
Enzyme Inhibitors chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1873-426X
- Volume :
- 543
- Database :
- MEDLINE
- Journal :
- Carbohydrate research
- Publication Type :
- Academic Journal
- Accession number :
- 38996783
- Full Text :
- https://doi.org/10.1016/j.carres.2024.109198