Synthesis of 2-(1-aminocyclopropyl)pyrrolidine-3,4-diol derivatives applying titanium-mediated reaction conditions

The titanium-mediated cyclopropanation reaction using Ti(O i Pr) 3Me/EtMgBr/BF 3·OEt 2 has been applied to various 2-cyanopyrrolidines for the synthesis of functionalized 2-(1-aminocyclopropyl)pyrrolidine-3,4-diol derivatives (dideoxyiminoalditols). Under the same experimental conditions the trans-5-azidomethyl-2-cyanopyrrolidine derivative was not cyclopropanated but reduced into the corresponding 5-amino-2-cyano derivative. After polyol deprotection 2-(1-aminocyclopropyl)pyrrolidine-3,4-diols were obtained and their inhibitory activity towards 13 glycosidases has been evaluated. (2 S,3 S,4 R,5 S)-2-(1-Aminocyclopropyl)-5-methylpyrrolidine-3,4-diol ( 38), which has the same absolute configuration as l-fucose, is a moderate ( IC 50=44 μM), but selective, inhibitor of α- l-fucosidase from human placenta. [Display omitted]