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ID: ALA1177655

Journal: Bioorg Med Chem

Title: Synthesis and inhibitory activities of novel C-3 substituted azafagomines: a new type of selective inhibitors of α-L-fucosidases.

Authors: Moreno-Clavijo E, Carmona AT, Moreno-Vargas AJ, Rodríguez-Carvajal MA, Robina I.

Abstract: 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.

CiteXplore: 20570156

DOI: 10.1016/j.bmc.2010.05.026