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

• Published in: Beilstein journal of organic chemistry Vol. 14; no. 1; pp. 2156 - 2162
• Main Authors: Bella, Maroš, Šesták, Sergej, Moncoľ, Ján, Koóš, Miroslav, Poláková, Monika
• Format: Journal Article
• Language: English
• Published: Germany Beilstein-Institut zur Föerderung der Chemischen Wissenschaften 17.08.2018; Beilstein-Institut
• Subjects: Alcohol; azasugars; Carbohydrates; Chemistry; Efficiency; Enzymes; Full Research Paper; Golgi apparatus; hydrolases; inhibitors; Mannosidase; Nitrogen; Oxidation; pyrrolidines; synthesis; Slovakia; synthesis; hydrolases; inhibitors; pyrrolidines; azasugars
• ISSN: 1860-5397; 2195-951X; 1860-5397
• DOI: 10.3762/bjoc.14.189

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 -(4-halobenzyl)polyhydroxypyrrolidines. An impact of the C-5 modification on the inhibition and selectivity against GH38 α-mannosidases from , the Golgi (GMIIb) and lysosomal (LManII) mannosidases and commercial jack bean α-mannosidase from 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.