Department of Chemistry, University of Michigan, 930N. University Avenue, Ann Arbor, MI, 48109, USA.
Higher College of the Russian Academy of Sciences, Mendeleev University of Chemical Technology, Miusskaya Square 9, Moscow, RU, 125047, Russia.
J Antibiot (Tokyo). 2019 Jun;72(6):437-448. doi: 10.1038/s41429-019-0172-1. Epub 2019 Apr 4.
This manuscript describes a single pot protocol for the selective introduction of unprotected sugars to the C3 position of the cardiotonic steroid strophanthidol. These reactions proceed with high levels of regiocontrol (>20:1 rr) in the presence of three other hydroxyl functionalities including the C19 primary hydroxyl group and could be applied to different sugars to provide the deprotected cardiac glycosides upon work up (5 examples, 77-69% yield per single operation). The selective glycosylation of the less reactive C3 position is accomplished by the use of traceless protection with methylboronic acid that blocks the C5 and C19 hydroxyls by forming a cyclic boronic ester, followed by in situ glycosylation and a work up with ammonia in methanol to remove the boronic ester and the carbohydrate ester protecting groups.
本文稿描述了一种将未保护的糖选择性引入到强心甾烯蟾毒配基的 C3 位的单釜法。在存在其他三个羟基官能团（包括 C19 伯羟基）的情况下，这些反应具有高区域选择性（>20:1 rr），并且可以应用于不同的糖，以在进行工作后提供未保护的强心苷（5 个实例，每个单步操作的产率为 77-69%）。通过使用硼酸三甲酯进行无痕迹保护，可以实现对反应性较低的 C3 位的选择性糖基化，硼酸三甲酯通过形成环状硼酸酯来封闭 C5 和 C19 羟基，然后进行原位糖基化，并用甲醇中的氨进行处理以去除硼酸酯和糖基酯保护基。
