Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Lebl, R; Thonhofer, M; Tysoe, C; Pabst, BM; Schalli, M; Weber, P; Paschke, E; Stütz, AE; Tschernutter, M; Windischhofer, W; Withers, SG.
A Morita-Baylis-Hillman based route to C-5a-chain-extended 4-epi-isofagomine type glycosidase inhibitors.
Carbohydr Res. 2017; 442(15):31-40
Doi: 10.1016/j.carres.2017.03.003
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Pabst Bettina
- Paschke Eduard
- Schalli Michael
- Tschernutter Marion
- Windischhofer Werner
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- Abstract:
- By Morita-Baylis-Hillman reaction of 2,3-O-isopropylidene-D-glyceraldehyde with α,β-unsaturated carbonyl as well as hetero analogous carbonyl compounds such as acrylonitrile, suitable precursors of isofagomine and of 4-epi-isofagomine are available. Elaboration of the structures by amine introduction, followed by intramolecular ring closure and subsequent hydroboration of the double bond provides 4-epi-isofagomine derivatives featuring chain extensions at C-5a which are determined by the structures of the carbonyl compounds employed. As an example, the synthesis of C-(5aR)- and C-(5aS)-5a-C-pentyl-4-epi-isofagomines, powerful inhibitors of β-galactosidases, is outlined. In line with reported data, the (C-5aR) epimer was found a highly potent experimental pharmacological chaperone for GM1-associated human lysosomal β-galactosidase mutant R201C. Copyright © 2017 Elsevier Ltd. All rights reserved.
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- Dose-Response Relationship, Drug -
- Enzyme Inhibitors - chemical synthesis
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- Glycoside Hydrolases - antagonists & inhibitors
- Glycoside Hydrolases - metabolism
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- Find related publications in this database (Keywords)
- Morita-Baylis-Hillman reaction
- 4-epi-isofagomine
- Glycosidase inhibitor
- Pharmacological chaperone