Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 West Green Street, Athens, Georgia 30602, United States.
Department of Chemistry, University of Georgia, 140 Cedar Street, Athens, Georgia 30602, United States.
J Org Chem. 2020 Dec 18;85(24):16035-16042. doi: 10.1021/acs.joc.0c01838. Epub 2020 Sep 23.
The preparation of glycosyl dibutyl phosphates in the 3-deoxy-d--oct-2-ulosonic acid (KDO) and pseudaminic acid series and their application to the formation of -glycosides are described. Both donors were obtained from the corresponding thioglycosides by treatment with dibutylphosphoric acid and -iodosuccinimide. As with the thioglycosides, both donors adopted very predominantly the strongly electron-withdrawing conformation of their side chains, which is reflected in the excellent equatorial selectivity of both donors in the formation of exemplary -glycosides. With respect to -glycoside formation on the other hand, contrasting results were observed: the KDO donor was either relatively unselective or selective for the formation of the axial -glycoside, while the pseudaminic acid donor was selective for the formation of the equatorial -glycoside. These observations are rationalized in terms of the greater electron-withdrawing ability of the azides in the pseudaminic acid donor compared to the corresponding acetoxy groups in the KDO series, resulting in a reaction through tighter ion pairs even at the S1 end of the general glycosylation mechanism. The contrast in the axial versus the equatorial selectivity between - and -glycosylation cautions against the extrapolation of models for S1-type glycosylation with weak nucleophiles for the explanation of -glycosylation.
描述了 3-脱氧-D--辛-2-酮酸（KDO）和假氨基糖酸系列中糖苷基二丁基磷酸酯的制备及其在β-糖苷形成中的应用。两种供体均通过二丁基磷酸和-碘代琥珀酰亚胺处理相应的硫代糖苷获得。与硫代糖苷一样，两种供体都非常强烈地采用了其侧链的强吸电子构象，这反映在两种供体在形成典型β-糖苷时的优异的非对映选择性。另一方面，对于β-糖苷的形成，观察到了对比鲜明的结果：KDO 供体对于轴向β-糖苷的形成要么相对无选择性，要么选择性高，而假氨基糖酸供体则选择性地形成非对映异构体β-糖苷。这些观察结果可以根据假氨基糖酸供体中叠氮化物的吸电子能力大于 KDO 系列中相应的乙酰氧基来合理化，即使在一般糖苷化机制的 S1 末端，反应也通过更紧的离子对进行。β-和β-糖苷化之间的轴向与非对映选择性的对比告诫人们，对于弱亲核试剂的 S1 型糖苷化模型，不能外推用于解释β-糖苷化。
