新加坡国立大学Koh, Ming Joo团队报道了天然糖的直接自由基功能化。相关研究成果于2024年6月19日发表于国际顶尖学术期刊《自然》。

天然存在的（天然）糖和碳水化合物含有许多反应活性相似的羟基。因此，化学家通常依靠费力的多步骤保护基团策略将这些可再生原料转化为试剂（糖基供体）来制备聚糖。将天然糖直接转化为复杂糖仍然是一个显著的挑战。

该文中，研究人员描述了一种从广泛可用的天然糖构建块中，实现位点和立体选择性化学糖基化的光诱导方法，该方法通过均裂（单电子）化学绕过了不必要的羟基掩蔽和操作。这一过程让人想起了自然，即其区域控制的瞬时糖基供体的产生，然后在光活化时与亲电试剂进行基于自由基的交叉偶联。

通过单糖和低聚糖的选择性异头功能化，这种无保护基的“帽和糖基化”方法提供了一系列代谢强健的糖基化合物的直接途径。由于其生物相容性，该方法被扩展到蛋白质的直接翻译后糖基化。

附：英文原文

Title: Direct radical functionalization of native sugars

Author: Jiang, Yi, Wei, Yi, Zhou, Qian-Yi, Sun, Guo-Quan, Fu, Xia-Ping, Levin, Nikita, Zhang, Yijun, Liu, Wen-Qiang, Song, NingXi, Mohammed, Shabaz, Davis, Benjamin G., Koh, Ming Joo

Issue&Volume: 2024-06-19

Abstract: Naturally occurring (native) sugars and carbohydrates contain numerous hydroxyl groups of similar reactivity1,2. Chemists, therefore, rely typically on laborious, multi-step protecting-group strategies3 to convert these renewable feedstocks into reagents (glycosyl donors) to make glycans. The direct transformation of native sugars to complex saccharides remains a notable challenge. Here we describe a photoinduced approach to achieve site- and stereoselective chemical glycosylation from widely available native sugar building blocks, which through homolytic (one-electron) chemistry bypasses unnecessary hydroxyl group masking and manipulation. This process is reminiscent of nature in its regiocontrolled generation of a transient glycosyl donor, followed by radical-based cross-coupling with electrophiles on activation with light. Through selective anomeric functionalization of mono- and oligosaccharides, this protecting-group-free ‘cap and glycosylate’ approach offers straightforward access to a wide array of metabolically robust glycosyl compounds. Owing to its biocompatibility, the method was extended to the direct post-translational glycosylation of proteins.

DOI: 10.1038/s41586-024-07548-0

Source: https://www.nature.com/articles/s41586-024-07548-0