Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 West Green Street, Athens, Georgia 30602, United States.
Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States.
J Am Chem Soc. 2020 Apr 29;142(17):7760-7764. doi: 10.1021/jacs.0c03215. Epub 2020 Apr 14.
The pseudosymmetric relationship of the bacterial sialic acid, pseudaminic acid, and 3-deoxy-d-manno-oct-2-ulosonic acid (KDO) affords the hypothesis that suitably protected KDO donors will adopt the conformation of their side chain and consequently be highly equatorially selective in their coupling reactions conducted at low temperature. This hypothesis is borne out by the synthesis, conformational analysis, and excellent equatorial selectivity seen on coupling of per--acetyl or benzyl-protected KDO donors in dichloromethane at -78 °C. Mechanistic understanding of glycosylation reactions is advancing to a stage at which predictions of selectivity can be made. In this instance, predictions of selectivity provide the first highly selective entry into KDO equatorial glycosides such as are found in the capsular polysaccharides of numerous pathogenic bacteria.
细菌唾液酸、假氨基糖酸和 3-脱氧-D-甘露辛-2-酮酸（KDO）的伪对称关系假设，适当保护的 KDO 供体将采用其侧链的构象，并且在低温下进行的偶联反应中具有高度赤道选择性。这一假设通过合成、构象分析以及在-78°C 的二氯甲烷中对全乙酰基或苄基保护的 KDO 供体的偶联反应中观察到的优异赤道选择性得到证实。糖基化反应的机制理解正在推进到可以进行选择性预测的阶段。在这种情况下，选择性预测为首次提供了进入 KDO 赤道糖苷的高度选择性入口，例如在许多致病性细菌的荚膜多糖中发现的糖苷。
