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

被引：16

作者：

Moreno-Clavijo, Elena ^{[1
]}

Carmona, Ana T. ^{[1
]}

Moreno-Vargas, Antonio J. ^{[1
]}

Rodriguez-Carvajal, Miguel A. ^{[1
]}

Robina, Inmaculada ^{[1
]}

机构：

[1] Univ Seville, Fac Chem, Dept Organ Chem, E-41012 Seville, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 13期

关键词：

Reductive hydrazination; Hexahydropyridazines; Azafagomines; alpha-L-Fucosidase inhibitors; GLYCOSIDASE INHIBITION; THERMOTOGA-MARITIMA; BETA-GLUCOSIDASE; STRUCTURAL BASIS; BINDING; IMINOCYCLITOLS; 1-AZAFAGOMINE; PURIFICATION; ISOFAGOMINE; MOLECULES;

D O I：

10.1016/j.bmc.2010.05.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-azafag-omine 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 alpha-L-fucosidases. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4648 / 4660

页数：13

共 60 条

[1] SYNTHESIS OF AND GLYCOSIDASE INHIBITION BY ALPHA-L-HOMOFUCONOJIRIMYCIN [J].