Leiden Institute of Chemistry, Leiden University , P.O. Box 9502, 2300 RA Leiden, The Netherlands.
J Org Chem. 2017 Dec 15;82(24):12992-13002. doi: 10.1021/acs.joc.7b02511. Epub 2017 Dec 1.
The development of effective protecting group chemistry is an important driving force behind the progress in the synthesis of complex oligosaccharides. Automated solid-phase synthesis is an attractive technique for the rapid assembly of oligosaccharides, built up of repetitive elements. The fact that (harsh) reagents are used in excess in multiple reaction cycles makes this technique extra demanding on the protecting groups used. Here, the synthesis of a set of oligorhamnan fragments is reported using the cyanopivaloyl (PivCN) ester to ensure effective neighboring group participation during the glycosylation events. The PivCN group combines the favorable characteristics of the parent pivaloyl (Piv) ester, stability, minimal migratory aptitude, minimal orthoester formation, while it can be cleaved under mild conditions. We show that the remote CN group in the PivCN renders the PivCN carbonyl more electropositive and thus susceptible to nucleophilic cleavage. This feature is built upon in the automated solid-phase assembly of the oligorhamnan fragments. Where the use of a Piv-protected building block failed because of incomplete cleavage, PivCN-protected synthons performed well and allowed the generation of oligorhamnans, up to 16 monosaccharides in length.
有效保护基团化学的发展是复杂寡糖合成进展的重要推动力。自动化固相合成是一种有吸引力的技术，可用于快速组装由重复单元组成的寡糖。由于在多个反应循环中过量使用（苛刻）试剂，因此对所用保护基团的要求更高。在这里，使用氰基戊酰基（PivCN）酯报告了一组低聚鼠李糖片段的合成，以确保在糖基化反应中有效进行邻基参与。PivCN 基团结合了母体特戊酰基（Piv）酯的有利特性，即稳定性、最小迁移趋势、最小邻酯形成，同时它可以在温和条件下裂解。我们表明，PivCN 中的远程 CN 基团使 PivCN 羰基更具正电性，从而易于亲核裂解。该特性在寡糖片段的自动化固相组装中得到了体现。在使用 Piv 保护基构建块时，由于不完全裂解而导致失败的情况下，PivCN 保护的合成子表现良好，并允许生成寡糖，最长可达 16 个单糖。
