Synthesis of 1-Deoxymannojirimycin from d-Fructose using the Mitsunobu Reaction.

Three different Mitsunobu reactions have been investigated for the synthesis of 1-deoxymannojirimycin (1-DMJ) from d-fructose. The highest yielding and most practical synthesis can be undertaken on a 10 g scale with minimal chromatography. In the key step, N , O -di-Boc-hydroxylamine reacts with methyl 1,3-isopropylidene-α-d-fructofuranose under Mitsunobu conditions to give 14 . Acidic hydrolysis affords nitrone 15 , which reduces quantitatively via catalytic hydrogenolysis to afford 1-DMJ ( 4 ) in 55% overall yield from d-fructose (cf. 37% for azide route and 29% for nosyl route).