Bioorganic & Medicinal Chemistry 2012-01-15

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

Julia Deschamp, Martine Mondon, Shinpei Nakagawa, Atsushi Kato, Dominic S Alonzi, Terry D Butters, Yongmin Zhang, Matthieu Sollogoub, Yves Blériot

Index: Bioorg. Med. Chem. 20 , 641-9, (2012)

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Abstract

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.Copyright © 2010 Elsevier Ltd. All rights reserved.