Stereoisomeric Imidazolo-Pentoses − Synthesis, Chiroptical Properties, and Evaluation as Glycosidase Inhibitors

• Published in: European journal of organic chemistry Vol. 2001; no. 7; pp. 1335 - 1347
• Main Authors: Tschamber, Théophile, Siendt, Hervé, Boiron, Arnaud, Gessier, François, Deredas, Dariusz, Frankowski, Andrzej, Picasso, Sylviane, Steiner, Heinz, Aubertin, Anne-Marie, Streith, Jacques
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 01.04.2001; WILEY‐VCH Verlag GmbH; Wiley
• Subjects: Azasugars; Chemistry; Chemistry, Organic; Circular dichroism; Glycosidase inhibitors; Imidazolo-piperidinoses; Physical Sciences; Science & Technology; ANALOGS; COLORIMETRIC ASSAY; BETA-D-GLUCOSAMINIDASE; GLYCOPROCESSING INHIBITORS; MECHANISMS; circular dichroism; NAGSTATIN; azasugars; DERIVATIVES; imidazolo-piperidinoses; glycosidase inhibitors
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/1099-0690(200104)2001:7<1335::AID-EJOC1335>3.0.CO;2-Z

The syntheses of all four imidazolo‐piperidino‐pentoses in the L‐series ent‐2 to ent‐5, and of three out of the four possible stereomers in the D‐series 3, 4, and 5, are reported. The linear imidazolo sugar precursors were prepared, either by double condensation of formamidine with protected aldohexoses, or by nucleophilic addition of a lithiated imidazole derivative to protected aldotetroses. Cyclisation of these linear imidazolo‐carbohydrates was performed by intramolecular SN2 reactions. These were followed by deprotection to the target molecules. The four pairs of opposite enantiomers showed pronounced mirror‐image‐type Cotton effects in their CD spectra. All stereomers of the D‐series show a negative rotatory power ([α]D), while the stereomers of the L‐series show a positive one. None of the eight imidazolo sugars inhibited the replication of HIV‐1. Some of them proved to be rather selective but only moderately potent inhibitors of α‐glycosidases, as determined by Michaelis‐Menten kinetics.