Synthetic studies towards a new scaffold, spirobicycloimidazoline

Abstract

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, (5 R,6 R,7 R,8 R)-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-α/β- d- gluco-6-enopyranoside via (1 R,2 S,3 S,4 R,5 S)-3,4-bis(benzyloxy)-2-(4-methoxybenzyloxy)-5-vinyl-cyclopentanol. The ring contraction of the 6-enopyranoside in the presence of zirconocene equivalent (‘Cp 2Zr’) reagent gave exclusively the corresponding cyclopentanol without cleavage of the PMB protecting group. In the course of the study, a new α-mannosidase inhibitor, (1 R,2 R,3 R,5 R)-5-amino-3-hydroxymethyl-cyclopentane-1,2-diol, was also discovered.