title: Skeletal rearrangement of seven-membered iminosugars: synthesis of (-)-adenophorine, (-)-1-epi-adenophorine and derivatives and evaluation as glycosidase inhibitors.
abstract: The mirror image of natural product (+)-adenophorine along with its 1-epi-, 1-homo-analogs and other derivatives have been synthesized and evaluated as glycosidase inhibitors. The synthetic strategy is based on the skeletal rearrangement of tetrahydroxylated C-alkyl azepanes obtained via a Staudinger/azaWittig/alkylation sequence starting from a sugar-derived azidolactol. Several organometallic species have been investigated for the alkylation step including organomagnesium, organolithium, organozinc, organoaluminum and organocerium reagents. While diallylzinc proved to be the most efficient to introduce an allyl substituent, disappointing results were obtained with the other organometallic species leading either to lower yields or no reaction. Enzymatic assays indicate that (-)-adenophorine is a moderate α-l-fucosidase inhibitor.
authors.affiliation: Université de Poitiers, Equipe Synthèse Organique, Groupe Glycochimie, UMR-CNRS 7285, IC2MP, 4 rue Michel Brunet, 86022 Poitiers, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Mondon
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lecornué
authors.forename: Jérôme
authors.initials: J
authors.lastname: Guillard
authors.forename: Shinpei
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Yves
authors.initials: Y
authors.lastname: Blériot
mesh_terms: D000478:Alkylation; D000818:Animals; D001234:Aspergillus niger / Q000201:enzymology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050111:Imino Sugars / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D012275:Oryza / Q000201:enzymology; D011485:Protein Binding; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013237:Stereoisomerism; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001372:Aza Compounds; D004791:Enzyme Inhibitors; D050111:Imino Sugars; C482663:adenophorine; D006026:Glycoside Hydrolases; D005644:alpha-L-Fucosidase
keywords: Adenophorine; Azepane; Glycosidase inhibition; Iminosugar; Natural product