Synthesis of aza-C-disaccharides (dideoxyimino-alditols C-linked to monosaccharides) and analogues

The first aza-C-disaccharide (D-azaMan-beta-CHz-(1 -> 6)-D-Man-alpha-OMe) that mimicks alpha-D-Manp-(1 -> 6)-alpha-D-ManOMe was made in 1994 by Johnson and coworkers. Several synthetic approaches to these disaccharide mimetics have been proposed. These are reviewed and compared. Several strategies rely on C-C bond forming reactions such as the Miyaura-Suzuki cross-coupling, the SmI2 Barbier reaction, the addition of acetylides to aldonolactones, the cross-aldol reaction or the Michael addition of 7-oxabicyclo[2.2.1]heptanone derivatives ('naked sugars'), with subsequent formation of the iminoalditol moieties. Other approaches use nitrogen-containing systems such as sugar-derived nitrones or iminoal-doses that are coupled by either Wittig olefinations, cross-aldol reactions or Takai-Oshima-Nozaki-Kishi reactions. When available, the conformational analysis of the aza-C-disaccharides, as well as their inhibitory activities toward glycosidases, will be summarized.