A Morita-Baylis-Hillman based route to C-5a-chain-extended 4-epi-isofagomine type glycosidase inhibitors
| Autor: | René Lebl, Bettina M. Pabst, Marion Tschernutter, Stephen G. Withers, Arnold E. Stütz, Patrick Weber, Eduard Paschke, Michael Schalli, Werner Windischhofer, Martin Thonhofer, Christina Tysoe |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Glycoside Hydrolases Double bond Stereochemistry Ring (chemistry) 01 natural sciences Biochemistry Analytical Chemistry Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound medicine Humans Enzyme Inhibitors chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry General Medicine 0104 chemical sciences Pharmacological chaperone Hydroboration 030104 developmental biology Intramolecular force Epimer Amine gas treating Acrylonitrile Lysosomes Imino Pyranoses medicine.drug |
| Zdroj: | Carbohydrate Research. 442:31-40 |
| ISSN: | 0008-6215 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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