All eight stereoisomeric D-glyconic-delta-lactams: synthesis, conformational analysis, and evaluation as glycosidase inhibitors.
An efficient and general synthetic route to all eight stereoisomeric D-glycono-delta-lactams has been developed. The strategy involves, as a key step, a stereodivergent delta-lactam formation with configurational retention or inversion at C-4 of a starting gamma-lactone to lead to two epimers of delta-lactam from one parent gamma-lactone. Conformations of eight glycono-delta-lactams were examined by X-ray crystallographic analysis and molecular modeling. Analyses of conformation and glycosidase-inhibition provide useful information for the design of new glycosidase inhibitors.
Nishimura
Y
Y
Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
Adachi
H
H
Satoh
T
T
Shitara
E
E
Nakamura
H
H
Kojima
F
F
Takeuchi
T
T
D000818:Animals; D001234:Aspergillus niger / Q000201:enzymology; D002236:Carbohydrate Conformation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008361:Mannosidases / Q000037:antagonists & inhibitors; D008956:Models, Chemical; D008958:Models, Molecular; D012441:Saccharomyces cerevisiae; D012908:Snails; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043323:alpha-Mannosidase; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D007769:Lactams; D006026:Glycoside Hydrolases; D008361:Mannosidases; D001617:beta-Glucosidase; D043323:alpha-Mannosidase