Synthesis of a bicyclic analog of l-iduronic acid adopting the biologically relevant 2S0 conformation

The synthesis of a bicyclic analogue of the naturally occurring α-l-iduronic acid locked in a biologically active 2S0 skewboat conformation is disclosed. The desired 2S0 conformation has been obtained by tethering the C-2 and C-5 carbon atoms of the sugar ring with a dimethyloxy bridge and confirmed by NMR and molecular modeling. The new mimic displays the exact hydroxyl pattern of α-l-iduronic acid, a major monosaccharide component of glycosaminoglycans and thus represents a closer mimic of the latter, compared to previously reported bicyclic analogs.Figure optionsDownload full-size imageDownload as PowerPoint slide

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide