Kim In Su, Kim Sin Jung, Lee Jae Koo, Li Qing Ri, Jung Young Hoon
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Carbohydr Res. 2007 Aug 13;342(11):1502-9. doi: 10.1016/j.carres.2007.04.021. Epub 2007 Apr 29.
A stereoselective approach for synthesizing (2R,5S)-dihydroxymethyl-(3R,4R)-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 degrees 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.
以2,3,4,6-四-O-苄基-D-甘露糖（7）为起始原料，通过七步反应实现了一种立体选择性合成（2R,5S）-二羟甲基-（3R,4R）-二羟基吡咯烷1（2,5-二脱氧-2,5-亚氨基-D-葡萄糖醇，DGDP）的方法。制备标题化合物1的关键步骤包括使用氯磺酰异氰酸酯（CSI）对肉桂基反式-1,2-多苄基醚5和6进行区域选择性和非对映选择性胺化反应，以及环化反应形成吡咯烷环。反式-1,2-多苄基醚5与CSI在甲苯中于0℃反应，以76%的产率得到相应的反式-1,2-氨基醇4作为主要产物，非对映选择性为16:1。这些反应的潜在机理可以用导致立体化学保持的邻基效应来解释。
