磺达肝癸钠关键中间体异构体的合成

Synthesis of Isomers of the Key Intermediate of Fondaparinux Sodium

为了控制磺达肝癸钠的质量,合成了中间体全保护戊糖(1)的两个异构体(1a,1b)。以含有葡萄糖醛酸和内醚糖的二糖为起始原料,脱氯乙酰基得到受体二糖,与单糖供体偶联得到三糖,开环、氨解、活化得到三糖供体,与还原端二糖受体偶联得全保护戊糖1(5个糖苷键构型次序为?-?-?-?-?)及其2个异构体1a(?-?-?-?-??和1b(?-?-?-?-?)。并经1H NMR和ESI-MS等确证了结构。

To conduct the quality control of fondaparinux sodium, two isomers（1a, 1b）of the fully protected pentasaccharide（1） which was the key intermediate of fondaparinux sodium were synthesized. The disaccharide which is composed of glucuronic acid and levoglucosan was used as the starting material to give the corresponding receptor by the removal of the chloracetyl group. The disaccharide receptor was coupled with a monosaccharide donor to give a trisaccharide. After ring-opening, ammonolysis and activization, the trisaccharide donor was obtained, which was coupled with the reducing end of the disaccharide receptor to provide 1（the configuration of glycosidic bond is α-β-α-α-α in sequence）and two isomers 1a（β-β-α-α-α ） and 1b（α-α-α-α-α）. The chemical structures were confirmed by ^1H NMR and ESI-MS.