Synthesis and inhibitory activities of novel C-3 substituted azafagomines: a new type of selective inhibitors of α-L-fucosidases.
The synthesis of a novel aminomethyl C-3 substituted L-fuco-azafagomine and of its C-6 epimer from D-lyxose is reported. The key step of the synthesis is the introduction of the biimino (-NH-NH-) moiety by reductive hydrazination of a 1-deoxy-ketohexose with tert-butyl carbazate. The 3-aminomethyl-azafagomine derivatives were used as lead compounds in the generation of libraries of novel types of derivatives by attaching different hydrophobic groups on the aminomethyl substituent through amide linkages. These polyhydroxylated hexahydropyridazines can be viewed as a new type of diaza-C-glycoside analogues having a biimino (-NH-NH-) moiety. The conformational analysis and the glycosidase inhibitory properties of all the new C-3 substituted azafagomines synthesized are also reported. Those having L-fuco configuration have shown a selective inhibition of α-L-fucosidases.
Moreno-Clavijo
Elena
E
Department of Organic Chemistry, Faculty of Chemistry, University of Seville, Profesor García González 1, E-41012 Seville, Spain.
Carmona
Ana T
AT
Moreno-Vargas
Antonio J
AJ
Rodríguez-Carvajal
Miguel A
MA
Robina
Inmaculada
I
D001372:Aza Compounds / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006834:Hydrazines / Q000737:chemistry; D050112:Imino Pyranoses / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008968:Molecular Conformation; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001372:Aza Compounds; D004791:Enzyme Inhibitors; D006834:Hydrazines; D050112:Imino Pyranoses; C518011:tert-butyl carbazate; C105643:fagomine; D005644:alpha-L-Fucosidase