Synthesis of 4a‐Carba‐ d ‐lyxofuranose Derivatives and Their Evaluation as Inhibitors of GH38 α‐Mannosidases

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.