Synthesis of (2 R,5 S)-dihydroxymethyl-(3 R,4 R)-dihydroxypyrrolidine (DGDP) via stereoselective amination using chlorosulfonyl isocyanate

A stereoselective approach for synthesizing (2 R,5 S)-dihydroxymethyl-(3 R,4 R)-dihydroxypyrrolidine 1 (2,5-dideoxy-2,5-imino- d-glucitol, DGDP) was achieved using a seven-step approach starting from 2,3,4,6-tetra- O-benzyl- d-mannose ( 7). Key steps for the preparation of the title compound 1 involved the regioselective and diastereoselective amination of the cinnamyl anti-1,2-polybenzyl ethers 5 and 6 using chlorosulfonyl isocyanate (CSI) and ring cyclization to form the pyrrolidine ring. The reaction between anti-1,2-polybenzyl ether 5 and CSI in toluene at 0 °C afforded the corresponding anti-1,2-amino alcohol 4 as a major product with a diastereoselectivity of 16:1 in 76% yield. The mechanism underlying these reactions may be explained by the neighboring-group effect leading to the retention of stereochemistry.