Abstract
The synthesis of the first examples of seven-membered ring iminoalditols, molecules displaying an extra hydroxymethyl substituent on their seven-membered ring compared to the previously reported polyhydroxylated azepanes, has been achieved from d-arabinose in 10 steps using RCM of a protected N-allyl-aminohexenitol as a key step. While the (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxy-azepane 10, a seven-membered ring analogue of fagomine, is a weak inhibitor of glycosidases, the (2R,3R,4R,5S,6S)-2-hydroxymethyl-3,4,5,6-tetrahydroxy-azepane 9 selectively inhibits green coffee bean alpha-galactosidase in the low micromolar range (Ki = 2.2 muM) despite a D-gluco relative configuration.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arabinose / chemistry
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Cellulases / antagonists & inhibitors
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Cellulases / metabolism
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Crystallography, X-Ray
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Cyclization
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Glycoside Hydrolase Inhibitors
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Glycoside Hydrolases / antagonists & inhibitors*
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Glycoside Hydrolases / metabolism
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Heterocyclic Compounds, 1-Ring / chemistry
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Imines / chemistry
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Magnetic Resonance Spectroscopy
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Molecular Conformation
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Molecular Structure
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Monosaccharides / chemistry
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Sugar Alcohols / chemistry
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alpha-Galactosidase / antagonists & inhibitors
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alpha-Galactosidase / metabolism
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alpha-Glucosidases / metabolism
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beta-Galactosidase / antagonists & inhibitors
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beta-Galactosidase / metabolism
Substances
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Enzyme Inhibitors
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Glycoside Hydrolase Inhibitors
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Heterocyclic Compounds, 1-Ring
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Imines
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Monosaccharides
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Sugar Alcohols
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Arabinose
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Cellulases
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Glycoside Hydrolases
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alpha-Glucosidases
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alpha-Galactosidase
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beta-Galactosidase