Towards a stable noeuromycin analog with a D-manno configuration: synthesis and glycosidase inhibition of D-manno-like tri- and tetrahydroxylated azepanes.
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.
Deschamp
Julia
J
UPMC Univ Paris 06, Institut Parisien de Chimie Moléculaire, UMR CNRS 7201, C-181, 4 place Jussieu F-75005 Paris, France.
Mondon
Martine
M
Nakagawa
Shinpei
S
Kato
Atsushi
A
Alonzi
Dominic S
DS
Butters
Terry D
TD
Zhang
Yongmin
Y
Sollogoub
Matthieu
M
Blériot
Yves
Y
D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006900:Hydroxylation; D008358:Mannose / Q000737:chemistry*
D001381:Azepines; D004791:Enzyme Inhibitors; C433123:noeuromycin; D006026:Glycoside Hydrolases; D005944:Glucosamine; D008358:Mannose