Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

Beilstein Journal of Organic Chemistry

卷:14

Maroš Bella¹  Monika Poláková¹  Sergej Šesták¹  Miroslav Koóš¹  Ján Moncoľ² 

[1] Department of Glycochemistry, Institute of Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, SK-845 38, Bratislava, Slovakia;

[2] Department of Inorganic Chemistry, Faculty of Chemical and Food Technology, Radlinského 9, SK-812 37 Bratislava, Slovakia;

关键词: azasugars;    hydrolases;    inhibitors;    pyrrolidines;    synthesis;   

DOI  :  10.3762/bjoc.14.189

来源: DOAJ

【 摘 要 】

A synthetic approach to 1,4-imino-L-lyxitols with various modifications at the C-5 position is reported. These imino-L-lyxitol cores were used for the preparation of a series of N-(4-halobenzyl)polyhydroxypyrrolidines. An impact of the C-5 modification on the inhibition and selectivity against GH38 α-mannosidases from Drosophila melanogaster, the Golgi (GMIIb) and lysosomal (LManII) mannosidases and commercial jack bean α-mannosidase from Canavalia ensiformis was evaluated. The modification at C-5 affected their inhibitory activity against the target GMIIb enzyme. In contrast, no inhibition effect of the pyrrolidines against LManII was observed. The modification of the imino-L-lyxitol core is therefore a suitable motif for the design of inhibitors with desired selectivity against the target GMIIb enzyme.

【 授权许可】

Unknown