Syntheses of 2-deoxy-2-fluoro mono- and oligo-saccharide glycosides from glycals and evaluation as glycosidase inhibitors.
Several fluorinated oligosaccharides, including 2-deoxy-2-fluoro derivatives of cellobiose, maltose, and maltotriose were synthesized by the action of fluorine or acetyl hypofluorite on the corresponding glycal peracetates. Temperature effects on the stereoselectivities of these reactions were examined. Addition of acetyl hypofluorite to several 2-substituted glycals in the gluco or galacto series gave 2,2-disubstituted arabino- or lyxo-hexose derivatives; 3,4,6-tri-O-acetyl-2-fluoro-D-glucal or the analogous galactal yielded 2-deoxy-2,2-difluoro arabino- or lyxo-hexose peracetates, whereas 2-acetoxy-3,4,6-tri-O-acetyl-D-glucal or the analogous galactal gave 2(R)-2-acetoxy-2-fluoro-arabino- or lyxo-hexose peracetates, respectively. 2-Acetamido-3,4,6-tri-O-acetyl-D-glucal gave 2(R)-2-acetamido-2-acetoxy-3,4,6-tri-O-acetyl-alpha-D-arabino-hexopyrano syl fluoride. 2,4-Dinitrophenyl 2-deoxy-2-fluoro-beta-cellobioside was an inactivator of the exoglucanase from Cellulomonas fimi while 2-deoxy-2-fluoro-alpha-maltosyl and alpha-maltotriosyl fluorides were slow substrates of human pancreatic alpha-amylase and rabbit muscle glycogen debranching enzyme, respectively.
McCarter
J D
JD
Department of Chemistry, University of British Columbia, Vancouver, Canada.
Adam
M J
MJ
Braun
C
C
Namchuk
M
M
Tull
D
D
Withers
S G
SG
D000085:Acetates; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003837:Deoxy Sugars / Q000138:chemical synthesis* / Q000494:pharmacology; D004952:Esters; D005461:Fluorine; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006027:Glycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000085:Acetates; D003837:Deoxy Sugars; D004952:Esters; D006027:Glycosides; D009005:Monosaccharides; D009844:Oligosaccharides; D005461:Fluorine; C040801:acetyl hypofluorite; D005959:Glucosidases; D006026:Glycoside Hydrolases