Syntheses of homologous omega-aminated 1-methoxyalkyl beta-D-glucopyranosides as potential beta-D-glucosidase inhibitors.
(R)- and (S)-2-Azido-1-methoxyethyl beta-D-glucopyranosides (16) and (17), (R)- and (S)-3-azido-1-methoxypropyl beta-D-glucopyranosides (18) and (19), (R,S)-4-azido-1-methoxybutyl beta-D-glucopyranoside (20), and (R,S)-5-azido-1-methoxypentyl beta-D-glucopyranoside (22) were synthesized from omega-substituted dimethyl acetals of acetaldehyde, propanal, butanal, and pentanal by trimethylsilyl triflate-catalysed transacetalation using 1-O-trimethysilyl 2,3,4,6-tetra-O-acetyl-beta-D-glucose (1) as acceptor. Most of the acetylated (R,S)-epimers could be resolved into pure compounds by column chromatography. Preliminary tests showed that the deacetylated acetal glucosides carrying omega-bromo, azido, or acetamido substituents in the aglycon are good substrates for beta-D-glucosidase from sweet almonds. The corresponding omega-amino derivatives of compounds 16, 19, 20, and 22, (R)-2-amino-1-methoxyethyl beta-D-glucopyranoside (23), (S)-3-amino-1-methoxypropyl beta-D-glucopyranoside (24), (R,S)-4-amino-1-methoxybutyl beta-D-glucopyranoside (25), and (R,S)-5-amino-1-methoxypentyl beta-D-glucopyranoside (26) proved almost completely resistant to beta-D-glucosidase. The stability of the glucosides against enzyme hydrolysis is dependent on the distance between the amino group and the anomeric center.
D000478:Alkylation; D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D005960:Glucosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006027:Glycosides / Q000138:chemical synthesis*; D007536:Isomerism; D010944:Plants / Q000201:enzymology; D013329:Structure-Activity Relationship; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors*
D000588:Amines; D005960:Glucosides; D006027:Glycosides; D005959:Glucosidases; D001617:beta-Glucosidase