ortho-Carborane-Modified N-Substituted Deoxynojirimycins

N-alkyl-deoxynojirimycins (DNMs) are an important class of glycoprocessing enzyme inhibitors. Our work on DNMs focuses on identifying potent and selective inhibitors of the human enzymes, glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA) and neutral glucosylceramidase (GBA2). We have previously reported on N-alkylated DNM derivatives bearing various hydrophobic head groups (aliphatic, aromatic, branched, cyclic). In this study we report effective procedures for the synthesis of ortho-carborane-modified DNMs and establish the inhibitory potency of six new DNM derivatives 3-8 against GCS, GBA and GBA2.