Synthesis of novel seven-membered carbasugars and evaluation of their glycosidase inhibition potentials

Here, we report the synthesis of five novel seven-membered carbasugar analogs.

Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters

A set of 6- to 24-valent clusters was constructed with terminal deoxynojirimycin (DNJ) inhibitory heads through C6 or C9 linkers by way of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions between mono- or trivalent azido-armed iminosugars and calix[8]arene scaffolds differing in their valency and their rigidity but not in their size. The power of multivalency to upgrade the inhibition potency of the weak DNJ inhibitor (monovalent DNJ Ki being at 322 and 188 µM for C6 or C9 linkers, respectively) was evaluated on the model glycosidase Jack Bean α-mannosidase (JBα-man). Although for the clusters with the shorter C6 linker the rigidity of the scaffold was essential, these parameters had no influence for clusters with C9 chains: all of them showed rather good relative affinity enhancements per inhibitory epitopes between 70 and 160 highlighting the sound combination of the calix[8]arene core and the long alkyl arms. Preliminary docking studies were performed to get insights into the preferred binding modes.

Synthesis and glycosidase inhibition of N-substituted derivatives of 1,4-dideoxy-1,4-imino-d-mannitol (DIM)

Four series of N-substituted DIMs have been synthesized and assayed against glycosidases to provide continuous and reliable inhibitory spectra.