Multigram-Scale Synthesisof 2,5-Dideoxy-2,5-imino‑d‑mannitol (DMDP)and 2,5-Dideoxy-2,5-imino‑d‑glucitol (DGDP)from d‑Fructose and l‑Sorbose Usinga Regioselective Appel Reaction

We report a practical 5 g scale stereoselective synthesis of the valuable iminosugar DMDP from d-fructose in only 7 synthetic steps and in a 70% overall yield, which doubles previously reported yields. This process requires only two chromatographic purification steps, taking advantage of a regioselective Appel reaction. The regioselective reaction has also been applied on a similar scale to prepare the C-2 diastereomer of DMDP, DGDP, from l-sorbose in 7 steps (two purifications) and 56% overall yield, albeit with diminished diastereomeric purity (d.r. 90:10). The C-5 regioselectivity has also been illustrated on d-psicose and d-tagatose, making this an attractive method for preparing pyrrolidine iminosugars or 5-thiosugars from ketopyranoses.