Biosynthetic studies on the alpha-glucosidase inhibitor acarbose: the chemical synthesis of dTDP-4-amino-4,6-dideoxy-alpha-D-glucose.
To study the biosynthesis of the pseudotetrasaccharide acarbose, dTDP-4-amino-4,6-dideoxy-alpha-D-glucose (3) was prepared from galactose in 16 steps. After initial protecting-group manipulations, the 6-position of galactose was deoxygenated by hydride displacement of a tosylate. Similarly a tosyl group at the 4-position was displaced upon reaction with sodium azide. Conversion of the resulting glycoside to a glycosyl phosphate was accomplished by reaction of a glycosyl trichloroacetimidate with dibenzyl phosphate. Subsequent removal of the benzyl protecting groups and reduction of the azide by hydrogenation and coupling with an activated nucleoside phosphate gave dTDP-4-amino-4,6-dideoxy-alpha-D-glucose.
Bowers
Simeon G
SG
Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
Mahmud
Taifo
T
Floss
Heinz G
HG
D020909:Acarbose / Q000378:metabolism* / Q000494:pharmacology; D000606:Amino Sugars / Q000138:chemical synthesis* / Q000378:metabolism; D003837:Deoxy Sugars / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D013379:Substrate Specificity; D013942:Thymine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000637:Transaminases / Q000378:metabolism; D014166:Transferases / Q000378:metabolism
D000606:Amino Sugars; D003837:Deoxy Sugars; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D013942:Thymine Nucleotides; C456723:dTDP-4-amino-4,6-dideoxy-glucose; D014166:Transferases; D000637:Transaminases; D020909:Acarbose