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Synthesis of 4a‐Carba‐ d ‐lyxofuranose Derivatives and Their Evaluation as Inhibitors of GH38 α‐Mannosidases
Author(s) -
Zajičková Mária,
Moncoľ Ján,
Šesták Sergej,
Kóňa Juraj,
Koóš Miroslav,
Bella Maroš
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201801586
Subject(s) - chemistry , mannosidase , stereochemistry , canavalia ensiformis , amino acid , enzyme , biochemistry
A synthetic approach to 4a‐carba‐ d ‐lyxofuranose derivatives starting from d ‐lyxose is described. The protected 4a‐carba‐β‐ d ‐lyxofuranose was employed as the key intermediate for the synthesis of 4a‐carba‐ d ‐lyxofuranose derivatives including novel 1‐amino‐1‐deoxy‐4a‐carba‐ d ‐lyxofuranoses. Synthesized 4a‐carba‐ d ‐lyxofuranoses were evaluated as inhibitors of GH38 α‐mannosidases, namely, the Golgi (GMIIb) and lysosomal (LManII) α‐mannosidases from Drosophila melanogaster and commercial Jack bean α‐mannosidase (JBMan) from Canavalia ensiformis . The biochemical evaluation revealed that only 1‐amino‐1‐deoxy‐4a‐carba‐β‐ d ‐lyxofuranose exhibited reasonable inhibitory activity against GMIIb (IC 50 = 200 µ m ). In addition, the results of biological evaluation were discussed by means of molecular modelling.