Martin T J, Brescello R, Toepfer A, Schmidt R R
Fakultät Chemie, Universität Konstanz, Germany.
Glycoconj J. 1993 Feb;10(1):16-25. doi: 10.1007/BF00731182.
The importance and requirements for catalytic activation of sialyl donors are discussed, leading to the acid sensitive phosphite and phosphate moiety, respectively, as leaving group and nitriles as solvent. Therefore, from readily available N-acetylneuraminic acid, derivative 1 with phosphochloridites 2a-f and Huenigs' base sialyl phosphites 3a-f were prepared and isolated in high yields. Oxidation of 3a,c with tert-butyl-hydroperoxide afforded the corresponding phosphates 4a,c. As expected, phosphites 3 could be activated in acetonitrile by catalytic amounts of TMSOTf; thus, from 3a-e as donors and lactose derivatives 8A,B as acceptors the ganglioside building blocks 9A and 9B, respectively, were obtained in good yields. The best results were obtained with diethyl phosphite derivative 3a as sialyl donor, which exceeded by far the results obtained with the corresponding phosphate derivative 4a. Trisaccharide 9B was transformed into known 9A and into the fully O-acetylated GM3-trisaccharide 10.
讨论了唾液酸供体催化活化的重要性和要求，分别导致酸敏感的亚磷酸酯和磷酸酯部分作为离去基团，以及腈作为溶剂。因此，由易得的N-乙酰神经氨酸，制备了亚磷酰氯2a-f的衍生物1和休尼希碱唾液酸亚磷酸酯3a-f，并以高产率分离得到。用叔丁基过氧化氢氧化3a,c得到相应的磷酸酯4a,c。正如预期的那样，亚磷酸酯3可以在乙腈中用催化量的三甲基甲磺酸三甲基硅酯活化；因此，以3a-e作为供体和乳糖衍生物8A,B作为受体，分别以良好的产率得到神经节苷脂构建块9A和9B。以亚磷酸二乙酯衍生物3a作为唾液酸供体得到了最佳结果，其结果远远超过了相应的磷酸酯衍生物4a。三糖9B被转化为已知的9A和完全O-乙酰化的GM3-三糖10。
