Synthesis of an ether-linked alkyl 5a-carba-beta-D-glucoside, a 5a-carba-beta-D-galactoside, a 2-acetamido-2-deoxy-5a-carba-beta-D-glucoside, and an alkyl 5a'-carba-beta-lactoside.
For the purpose of providing biologically stable building blocks for the biocombinatorial synthesis using a living cell, some ether-linked alkyl 5a-carba-beta-D-glycoside primers were prepared. The key step of the synthesis was coupling of 1-bromo-n-alkanes with the 1-OH unprotected derivatives of 5a-carba-sugar analogues of D-glucose, D-galactose, and 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine), in DMF in the presence of sodium hydride. Alternatively, alkyl carba-lactoside was synthesized by incorporation of a 5a-carba-beta-D-galactose residue into the 4-position of dodecyl beta-D-glucopyranoside. A strong and specific inhibition of beta-galactosidase (K(i) 0.67 microM, bovine liver) was found for dodecyl 5a-carba-beta-D-galactopyranoside.
Ogawa
Seiichiro
S
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, Yokohama, 223-8522 Japan. ogawa@bio.keio.ac.jp
Aoyama
Hiroshi
H
Sato
Toshinori
T
D000818:Animals; D002417:Cattle; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D004987:Ethers / Q000737:chemistry; D005697:Galactosides / Q000138:chemical synthesis; D005960:Glucosides / Q000138:chemical synthesis; D006027:Glycosides / Q000138:chemical synthesis*; D009005:Monosaccharides / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors
C438934:C-glycoside; D004791:Enzyme Inhibitors; D004987:Ethers; D005697:Galactosides; D005960:Glucosides; D006027:Glycosides; D009005:Monosaccharides; C008245:lactosides; D001616:beta-Galactosidase