Malle Birgitte M, Lundt Inge, Wrodnigg Tanja M
Department of Chemistry, Technical University of Denmark (DTU), Building 201, DK-2800, Kgs. Lyngby, Denmark.
Org Biomol Chem. 2008 May 21;6(10):1779-86. doi: 10.1039/b719631h. Epub 2008 Mar 28.
1-Deoxymannojirimycin (8c) was synthesised from 2-amino-6-bromo-2,6-dideoxy-D-mannono-1,4-lactone (7) by intramolecular direct displacement of the C-6 bromine employing non-aqueous base treatment followed by reduction of the intermediate methyl ester. Likewise, using aqueous base at pH 12, ring closure took place by 5-exo attack on the 5,6-epoxide leading to 2,5-dideoxy-2,5-imino-L-gulonic acid (9b), which was reduced to 2,5-dideoxy-2,5-imino-D-glucitol (9b). The method was further applied to 2-amino-6-bromo-2,6-dideoxy-D-galacto- as well as D-talo-1,4-lactones (14 and 15). However, only the corresponding six-membered ring 1,5-iminuronic acid mimetics, namely (2R,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-galactonic acid, 16) and (2S,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-talonic acid, 17), were obtained. The corresponding enantiomers, L-galacto- as well as L-talo-2-amino-6-bromo-2,6-dideoxy-1,4-lactones ent-14 and ent-15, reacted accordingly to give the D-galacto- and L-altro-1,5-iminuronic acid mimetics, (2S,3S,4R,5S)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-L-galactonic acid, ent-16) and (2R,3S,4R,5S)-3,4,5-trihydroxypipecolic acids (2,6-dideoxy-2,6-imino-L-talonic acid, ent-17), respectively.
1-脱氧甘露基肌醇（8c）由2-氨基-6-溴-2,6-二脱氧-D-甘露糖-1,4-内酯（7）合成，通过非水碱处理分子内直接取代C-6位溴，随后还原中间的甲酯。同样，在pH 12的水性碱条件下，通过对5,6-环氧化物进行5-外向进攻发生环化反应，生成2,5-二脱氧-2,5-亚氨基-L-古洛糖酸（9b），将其还原得到2,5-二脱氧-2,5-亚氨基-D-葡萄糖醇（9b）。该方法进一步应用于2-氨基-6-溴-2,6-二脱氧-D-半乳糖-以及D-塔罗糖-1,4-内酯（14和15）。然而，仅得到了相应的六元环1,5-亚氨基糖醛酸类似物，即(2R,3R,4S,5R)-3,4,5-三羟基哌啶酸（2,6-二脱氧-2,6-亚氨基-D-半乳糖酸，16）和(2S,3R,4S,5R)-3,4,5-三羟基哌啶酸（2,6-二脱氧-2,6-亚氨基-D-塔罗糖酸，17）。相应的对映体，L-半乳糖-以及L-塔罗糖-2-氨基-6-溴-2,6-二脱氧-1,4-内酯对映体ent-14和ent-15，相应地反应，分别得到D-半乳糖-和L-阿卓糖-1,5-亚氨基糖醛酸类似物，(2S,3S,4R,5S)-3,4,5-三羟基哌啶酸（2,6-二脱氧-2,6-亚氨基-L-半乳糖酸，对映体-16）和(2R,3S,4R,5S)-3,4,5-三羟基哌啶酸（2,6-二脱氧-2,6-亚氨基-L-塔罗糖酸，对映体-17）。
