Convenient synthesis and evaluation of glycosidase inhibitory activity of alpha- and beta-galactose-type valienamines, and some N-alkyl derivatives.
Valienamine analogues having alpha- and beta-galactose-type structures were synthesized by racemic modification from (1SR,2RS,3SR)-6-methylenecyclohex-4-ene-1,2,3-triol. Four N-alkyl derivatives of the beta-anomer were readily prepared selectively by treatment of key intermediate 2,6-di-O-acetyl-3,4-O-isopropylidene-5a-carba-alpha- and beta-l-arabino-hex-5(5a)-enopyranosyl bromides with alkyl amines. All compounds were assayed for inhibitory activity against six glycosidases, and the N-dodecyl derivative was shown to be a very strong inhibitor of beta-galactosidase (IC(50) 0.01 microM, bovine liver).
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, Yokohama, 223-8522 Japan. ogawa@bio.keio.ac.jp
Seiichiro
S
Ogawa
Yuko
Y
Sakata
Naoyuki
N
Ito
Maiko
M
Watanabe
Kazuya
K
Kabayama
Masayoshi
M
Itoh
Takashi
T
Korenaga
D000818:Animals; D002417:Cattle; D053138:Cyclohexenes; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005690:Galactose / Q000138:chemical synthesis* / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006595:Hexosamines / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008099:Liver / Q000201:enzymology; D010944:Plants / Q000201:enzymology; D013329:Structure-Activity Relationship
D053138:Cyclohexenes; D004791:Enzyme Inhibitors; D006595:Hexosamines; C030791:valienamine; D006026:Glycoside Hydrolases; D005690:Galactose