From D-glucose to enantiomerically pure cycloctanoses. The glycosidase inhibitory capacity of medium-ring carbasugars.
Exhaustive dihydroxylation of the pair of cyclooctadienols consisting of 4 and 5, which are available in enantiomerically pure form from d-glucose, resulted in the formation of two diastereomeric tetraols in each case. The difference in polarity of the 6/7 and 8/9 pairs facilitated their chromatographic separation. Ensuing acetylation and PMB deprotection allowed for the assignment of relative (and ultimately absolute) stereochemistry to the resulting monohydric alcohols on the basis of J(HH) analysis of their (1)H NMR spectra. The highly functionalized exomethylenecyclooctanes 14-17, which were derived by periodinane oxidation and Wittig olefination, were further elaborated by hydroboration and global deprotection. The eight members of the cyclooctanose family of carbasugars and their precursor intermediates consistently showed patterns of J(HH) values in line with the contiguous stereochemical relationships. Also assayed was their specific inhibitory behavior toward glycosidases.
Paquette
Leo A
LA
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA. paquette@chemistry.ohio-state.edu
Moura-Letts
Gustavo
G
Wang
George Peng
GP
D054329:Carbasugars / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D034242:Cyclooctanes / Q000138:chemical synthesis / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D054329:Carbasugars; D034242:Cyclooctanes; D006026:Glycoside Hydrolases; D005947:Glucose