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.
UPMC Univ Paris 06, Institut Parisien de Chimie Moléculaire, UMR CNRS 7201, C-181, 4 place Jussieu F-75005 Paris, France.
Julia
J
Deschamp
Martine
M
Mondon
Shinpei
S
Nakagawa
Atsushi
A
Kato
Dominic S
DS
Alonzi
Terry D
TD
Butters
Yongmin
Y
Zhang
Matthieu
M
Sollogoub
Yves
Y
Blériot
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