1,3,4,6-四-O-乙酰基-2-O-三氟甲磺酰基-β-D-甘露吡喃糖的改进合成

An Improved Synthesis of 1,3,4,6-Tetra-O-acetyl-2-O-trifluoromethane Sulfonyl-β-D-mannopyranose

以D-甘露糖(Ⅰ)为原料,经3步(文献4步)反应,改进合成了1,3,4,6-四-O-乙酰基-2-O-三氟甲基磺酰基-β-D-甘露吡喃糖(Ⅳ),以Ⅰ计总摩尔收率为15.8%,高于文献[2004年,Toyokuni等]报道的实验平均值14.0%,HPLC纯度≥99.0%,单批次合成周期缩短为4～5 d,合成效率较文献[2004年,Toyokuni等]方法的7 d有显著提高,单批次制备Ⅳ达到100 g级水平。首先,Ⅰ在I2存在下与过量乙酸酐进行乙酰化反应,得到接近定量产率的1,2,3,4,6-五-O-乙酰基-D-甘露吡喃糖(Ⅱ);然后Ⅱ进一步在乙酸溶剂中与PBr3和乙酸钠水溶液分阶段进行溴化—水解"一锅法"反应,稳定获得了1,3,4,6-四-O-乙酰基-β-D-甘露吡喃糖(Ⅲ),单步摩尔收率为20.0%,产物的HPLC纯度≥98.0%;进一步用三乙胺作缚酸剂,在二氯甲烷溶剂中,三氟甲磺酸酐与Ⅲ在-20～-15℃反应,得目标化合物Ⅳ。

The synthesis of 1,3,4,6-tetra-O-aeetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose was investigated by using a three-step improved process from the starting material D-mannose（Ⅰ）. The total molar yield of 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose （Ⅳ ） was increased from 14.0% [ an average value from the results of Toyokuni et al（2004 ） 3, to 15.8% based on （ Ⅰ ）, and the HPLC purity was higher than 99.0%. The total synthesis period was reduced from 7 days [ according to the results of Toyokuni et al （2004） ] to 4 or 5 days. The synthesis of Ⅳ was realized in 100 g/batch scale. Thus, the acetylation of Ⅰ was first conducted in Ac2O at the presence of 12, and 1,2,3,4,6-penta-O-acetyl-D-mannopyranose （ 11 ） was separated with almost a quantitative yield.Then, Ⅱ reacted with PBr3, and subsequently the hydrolysis was carried out by using CH3COONa aqueous solution. 1,3,4,6-tetra-O-acetyl-/3-D-mannopyranose（Ⅲ） was recovered with a molar yield of 20. 0%. The HPLC purity was over 98%. Finally, at the presence of Et3N in the solvent CH2Cl2, the target molecule （ Ⅳ ） was prepared by reacting Ⅲ with trifluoromethanesulfonic anhydride at - 20 ℃ to -15 ℃.