Towards a stable noeuromycin analog with a D-manno configuration: synthesis and glycosidase inhibition of D-manno-like tri- and tetrahydroxylated azepanes.

Journal article

Noeuromycin is a highly potent albeit unstable glycosidase inhibitor due to its hemiaminal function. While stable D-gluco-like analogs have been reported, no data are available for D-manno-like structures. A series of tri- and tetrahydroxylated seven-membered iminosugars displaying either a D-manno-or a L-gulo-like configuration, were synthesized from methyl α-D-mannopyranoside using a reductive amination-mediated ring expansion as the key step. Screening towards a range of commercial glycosidases demonstrated their potency as competitive glycosidase inhibitors while cellular assay showed selective albeit weak glycoprotein processing mannosidase inactivation.

Authors: Deschamp, J; Mondon, M; Nakagawa, S; Kato, A; Alonzi, D

• Publication status: Published
• Journal: Bioorganic and medicinal chemistry
• Volume: 20
• Issue: 2
• Pages: 641-649
• Publication date: 2012-01-01
• DOI: 10.1016/j.bmc.2010.09.053
• EISSN: 1464-3391
• ISSN: 0968-0896
• Language: English
• Keywords: Enzyme Inhibitors; Azepines; Mannose; Glycoside Hydrolases; Hydroxylation; Glucosamine