General Methods for Iminosugar Synthesis

Laura      Cipolla; Barbara      La Ferla; Francesco      Nicotra

Abstract

Recent iminosugar syntheses starting both from commercially available sugars and non-glycidic precursors, are reported in this article. Exploiting carbohydrate starting materials, different synthetic approaches are described, mainly based on the introduction of an amino function in the sugar skeleton and the subsequent aminocyclization in order to generate the piperidine or pyrrolidine ring. The aminocyclization has been performed in different ways: reductive amination of azidoketones, intramolecular amino group attack on leaving groups and activated double bonds. In some cases one-pot amination and cyclization have been performed using ammonia or a primary amine and a di-functionalised sugar. Bicyclic compounds have also been obtained through these procedures. Starting from non-carbohydrate precursors, the nitrogen containing cycle, already present or easily obtained by Diels-Alder reactions, has been variously functionalised and stereo-differentiated by asymmetric induction or by resolution of the racemate. The syntheses of a variety of innovative structures, such as 1-N-iminosugars, iminosugars with two nitrogen atoms in the ring, iminosugars incorporating a guanidine function, imidazole-, triazole- and tetrazolefused iminosugars, sugar-like aza-, oxa-, and thio-indolizidines, are reported. Finally the synthesis of glycoconjugate-related iminosugars, where the “pseudoanomeric” centre is linked to amino acid or peptide residues, and iminosugar phosphonates and nucleosides have been reviewed.

Keywords: iminosuger synthesis, polyhydroxylated piperidines, pseudoanomeric centre, iminosugar phosphonates, iminosugar

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