gamma-Aminoalcohol rearrangement applied to pentahydroxylated azepanes provides pyrrolidines epimeric to homoDMDP

• Published in: Organic & biomolecular chemistry Vol. 13; no. 11; pp. 3446 - 3456
• Main Authors: Jagadeesh, Y., Tran, A. T., Luo, B., Auberger, N., Desire, J., Nakagawa, S., Kato, A., Zhang, Y., Sollogoub, M., Bleriot, Y.
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 01.01.2015; Royal Society of Chemistry
• Subjects: alpha-Glucosidases - metabolism; Amino Alcohols - chemistry; Azepines - chemistry; Catalysis; Chemical Sciences; Chemistry; Chemistry, Organic; Glycoside Hydrolase Inhibitors - chemical synthesis; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Imino Pyranoses - chemical synthesis; Imino Pyranoses - chemistry; Imino Pyranoses - pharmacology; Mannitol - analogs & derivatives; Mannitol - chemical synthesis; Mannitol - chemistry; Mannitol - pharmacology; Molecular Structure; Physical Sciences; Pyrrolidines - chemical synthesis; Pyrrolidines - chemistry; Science & Technology; Structure-Activity Relationship; 4-METHOXYBENZYLIDENE ACETALS; GLYCOSIDASE; ALPHA-MANNOSIDASE; POLYHYDROXYLATED PYRROLIDINE; 2,5-DIDEOXY-2,5-IMINO-D-MANNITOL DMDP; INHIBITORS; 7-MEMBERED IMINOCYCLITOLS; CONCISE SYNTHESIS; MIMICKING MONOSACCHARIDES; POLYHYDROXYAZEPANES
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c5ob00050e

A series of pentahydroxylated pyrrolidines, displaying five contiguous stereogenic centres and epimeric to alpha-glucosidase inhibitor homoDMDP, have been synthesized. The key step involves gamma-aminoalcohol rearrangement applied to polyhydroxylated azepanes. These five-membered iminosugars demonstrate micromolar inhibition of glycosidases.