Department of Chemistry , University of Toronto , 80 St. George St. , Toronto , ON M5S 3H6 , Canada.
J Org Chem. 2019 Jan 18;84(2):900-908. doi: 10.1021/acs.joc.8b02792. Epub 2019 Jan 8.
Sulfated carbohydrates have been implicated in diverse biological processes, with the position and extent of sulfation of a glycoside often playing important roles in determining the affinity and specificity of its binding to a biomolecular partner. Methods for the site-selective introduction of sulfate groups to carbohydrates are thus of interest. Here, we describe the development of a diarylborinic acid-catalyzed protocol for selective sulfation of pyranoside derivatives at the equatorial position of a cis-1,2-diol group. This method, which employs the sulfur trioxide-trimethylamine complex as the electrophile, has been employed for installation of a sulfate group at the 3-position of a range of galacto- and mannopyranosides, including substrates having a free primary OH group. By using a full equivalent of the diarylborinic acid, selective syntheses of more complex monosulfated glycosides, namely, a 3'-sulfolactose derivative and 3'-sulfo-β-galactosylceramide, have been accomplished. Preliminary kinetics experiments suggested that the catalyst resting state is a tetracoordinate diarylborinic ester that reacts with the SO complex in the turnover-limiting step. Catalyst inhibition by the pyranoside sulfate product and trialkylamine byproduct of the reaction was demonstrated.
硫酸化碳水化合物在多种生物过程中都有涉及，糖苷中硫酸化的位置和程度通常在确定其与生物分子伴侣结合的亲和力和特异性方面起着重要作用。因此，具有选择性地向碳水化合物中引入硫酸基团的方法引起了人们的兴趣。在这里，我们描述了一种二芳基硼酸催化的方案，用于在顺-1,2-二醇基团的赤道位置选择性地对吡喃糖苷衍生物进行硫酸化。该方法使用三氧化硫-三甲胺复合物作为亲电试剂，已用于在一系列半乳糖和甘露糖苷的 3-位上安装硫酸基团，包括具有游离伯羟基的底物。通过使用全当量的二芳基硼酸，可以选择性地合成更复杂的单硫酸化糖苷，即 3'-硫酸乳糖衍生物和 3'-硫酸-β-半乳糖神经酰胺。初步动力学实验表明，催化剂的静止状态是一个四配位的二芳基硼酸酯，它在周转限制步骤中与 SO 复合物反应。反应的吡喃糖苷硫酸盐产物和三烷基胺副产物对催化剂的抑制作用得到了证明。
