Synthetic studies towards a new scaffold, spirobicycloimidazoline.
A new scaffold consisting of a carbocycle and a substituted imidazoline in an orthogonal arrangement was synthesized as a potential specific inhibitor of glycosidases. The spirobicycloimidazoline, (5R,6R,7R,8R)-8-(hydroxymethyl)-2-phenyl-1,3-diazaspiro[4.4]non-1-ene-6,7-diol, was synthesized from methyl 2-O-p-methoxybenzyl-3,4-di-O-benzyl-alpha/beta-D-gluco-6-enopyranoside via (1R,2S,3S,4R,5S)-3,4-bis(benzyloxy)-2-(4-methoxybenzyloxy)-5-vinyl-cyclopentanol. The ring contraction of the 6-enopyranoside in the presence of zirconocene equivalent ('Cp(2)Zr') reagent gave exclusively the corresponding cyclopentanol without cleavage of the PMB protecting group. In the course of the study, a new alpha-mannosidase inhibitor, (1R,2R,3R,5R)-5-amino-3-hydroxymethyl-cyclopentane-1,2-diol, was also discovered.
Nakahara
Tatsuto
T
Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Yokohama, Japan.
Okamoto
Naoki
N
Suzuki
Katsuhiko
K
Kanie
Osamu
O
D003517:Cyclopentanes / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D048289:Imidazolidines / Q000138:chemical synthesis*; D013141:Spiro Compounds / Q000138:chemical synthesis*; D043323:alpha-Mannosidase / Q000037:antagonists & inhibitors
C531223:5-amino-3-hydroxycyclopentane-1,2-diol; C531222:8-(hydroxymethyl)-2-phenyl-1,3-diazaspiro(4.4)non-1-ene-6,7-diol; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D048289:Imidazolidines; D013141:Spiro Compounds; D006026:Glycoside Hydrolases; D043323:alpha-Mannosidase