Search

Iminosugars are an important class of natural products and have been subject to extensive studies in organic synthesis, bioorganic chemistry and medicinal chemistry, yet only a limited number of these studies are on glycosylated iminosugars. Here, a general route of synthesis is presented towards glycosylated 1‐deoxynojirimycin derivatives based on the oxidation–reductive amination protocol that in the past has also been shown to be a versatile route towards 1‐deoxynojirimycin. The strategy can be applied on commercial disaccharides, as shown in four examples, as well as on disaccharides that are not commercially available and are synthesized for this purpose, as shown by a fifth example. The synthesis of five deoxynojirimycin‐configured aza‐disaccharides, starting from their corresponding disaccharides and featuring a double reductive amination on 5‐keto‐aldehydes, that returns the stereochemistry of the reducing end d‐glucopyranose is presented. As starting materials disaccharides, which are available in bulk, can be used, and alternatively be obtained by chemical synthesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The synthesis of a focussed library of sphingolipids differing in the number and position of 13C labels is described. The synthesised sphingolipids differ in substitution at both the sphingosine amine (either palmitoylated or unmodified) and the sphingosine primary hydroxyl (unmodified or glycosylated). Moreover, 13C atoms are incorporated into either the sphingosine or the palmitate moiety, or both. This set of compounds is intended for use in relative quantitative lipidomics studies to gain insight into sphingolipid metabolism in healthy and diseased (lysosomal storage disorders) patients and animal models. [ABSTRACT FROM AUTHOR]

We report the tandem Staudinger/aza-Wittig/Ugi three-component reaction mediated synthesis of a 64-member compound library of aza-C-glycosides. The library is composed of four pyrrolidine and three piperidine scaffolds, onto which a number of functional groups is grafted to form seven sublibraries. Variation in the library is achieved by transformation of two pentoses and a hexose into the corresponding 4-azidopentanal and 5-azidohexanal derivatives as precursors for the Staudinger/aza-Wittig process. Further variation is achieved by using different isocyanides as well as protective- and functional-group manipulations on the fully protected Ugi-3CR intermediates. Preliminary biological evaluation of the compound library revealed several low micromolar inhibitors of human acid glucosylceramidase. [ABSTRACT FROM AUTHOR]