Crich David, Li Wenju
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061, USA.
J Org Chem. 2007 Mar 30;72(7):2387-91. doi: 10.1021/jo062431r. Epub 2007 Mar 6.
An N-acetyl-5-N,4-O-carbonyl-protected thiosialoside donor, the structure of which has been defined through X-ray crystallography, was prepared and tested in couplings to a wide range of acceptors. This donor gives excellent yields and alpha-selectivities in linking with various primary alkyl and carbohydrate acceptors under the N-iodosuccinimide and trifluoromethanesulfonic acid in situ activation method at -40 degrees C in dichloromethane. The favorable affect of the oxazolidinone substructure for alpha-sialylation is illustrated by a comparison study with a N,N-diacetylsialyl donor, which exhibited inferior yields and alpha-selectivities. The sialylation selectivity is independent of the anomeric configuration of the donor, but is highly related to the reaction temperature under the NIS/TfOH activation method. In contrast to the NIS/TfOH method, the Ph2SO/Tf2O promotion gives beta-selective couplings in dichloromethane. The oxazolidinone of the N-acetyl-5-N,4-O-carbonyl protected sialosides, both alpha- and beta-anomers, could be cleaved cleanly by treatment with sodium methoxide under mild conditions without removal of the acetamide.
制备了一种通过X射线晶体学确定其结构的N-乙酰基-5-N,4-O-羰基保护的硫代唾液酸苷供体，并在与多种受体的偶联反应中进行了测试。在二氯甲烷中于-40℃采用N-碘代琥珀酰亚胺和三氟甲磺酸原位活化方法时，该供体与各种伯烷基和碳水化合物受体连接时能给出优异的产率和α-选择性。通过与N,N-二乙酰基唾液酸供体的比较研究表明，恶唑烷酮亚结构对α-唾液酸化有有利影响，后者表现出较差的产率和α-选择性。唾液酸化选择性与供体的端基构型无关，但在NIS/TfOH活化方法下与反应温度高度相关。与NIS/TfOH方法相反，Ph2SO/Tf2O促进反应在二氯甲烷中给出β-选择性偶联。N-乙酰基-5-N,4-O-羰基保护的唾液酸苷的恶唑烷酮，无论是α-还是β-异头物，在温和条件下用甲醇钠处理均可干净地裂解，而无需除去乙酰胺。
