Synthesis of 2-(1-aminocyclopropyl)pyrrolidine-3,4-diol derivatives applying titanium-mediated reaction conditions
The titanium-mediated cyclopropanation reaction using Ti((OPr)-Pr-i)(3)Me/EtMgBr/BF3 center dot OEt2 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. (2S,3S,4R,5S)-2-(1-Aminocyclopropyl)-5-methylpyrrolidine-3,4-diol (38), which has the same absolute configuration as L-fucose, is a moderate (IC50=44 mu M), but selective, inhibitor of alpha-L-fucosidase from human placenta. (C) 2011 Elsevier Ltd. All rights reserved.
Keywords: alpha-L-Fucosidase inhibition ; 2-Cyanopyrrolidine ; Dideoxyiminoalditols ; Cyclopropylamine ; Titanium ; Kulinkovich reaction ; L-Fucosidase Inhibitors ; Glycosidase Inhibitors ; Alpha-Fucosidase ; Pyrrolidines ; Discovery ; Potent ; Cyclopropylamines ; Osteoarthritis ; Access ; Series
Record created on 2012-04-19, modified on 2016-08-09