中国科学院昆明植物研究所肖国志研究团队报道了模块化和一锅立体选择性糖基化策略，实现灵芝多糖全合成壬二酸十糖基序。相关研究成果发表在2024年6月11日出版的《美国化学会杂志》。

药用真菌灵芝多糖是治疗各种疾病的重要辅助治疗剂，包括白细胞减少症和造血损伤。然而，从灵芝多糖中合成长、支链和复杂的碳水化合物链仍然是化学合成中一项具有挑战性的任务。

该文中，研究人员首次报道了以具有不同生物活性的灵芝多糖GSPB70-S为原料，在糖基邻位-（1-henyvinyl）苯甲酸酯的基础上，通过一锅立体选择性糖基化策略，模块化化学合成九碳十糖基序，这不仅加快了碳水化合物的合成，而且减少了化学浪费，避免了硫代糖苷一锅糖基化固有的糖苷配基转移问题。

合成路线还强调了以下关键步骤：（1）基于预活化的一锅糖基化，通过试剂N-甲基-N-苯基甲酰胺调节，高度立体选择性地构建几个1,2-顺式-糖苷键，包括三个α-d-GlcN-（1→4）键和一个α-d-Gal-（1→4.）键；（2） 通过糖基N-苯基三氟乙酰亚胺酯、糖基邻炔基苯甲酸酯和糖基邻-（1-henyvinyl）苯甲酸酯的战略性组合，在各种直链和支链聚糖片段中的1,2-反式-糖苷键的正交一锅组装；和（3）最终的[1 × 4 + 15] Yu糖基化，用于高效组装nona-decasaccharide靶标。此外，还制备了4聚体、5聚体和6聚体的较短序列，用于结构-活性关系生物学研究。

目前的工作表明，这种一锅立体选择性糖基化策略可以提供一种可靠而有效的方法，来简化具有许多1,2-顺式-糖苷键的长、支链和复杂碳水化合物的化学合成。

附：英文原文

Title: Total Synthesis of Nona-decasaccharide Motif from Ganoderma sinense Polysaccharide Enabled by Modular and One-Pot Stereoselective Glycosylation Strategy

Author: Zhiyuan Chen, Guozhi Xiao

Issue&Volume: June 11, 2024

Abstract: Polysaccharides from a medicinal fungus Ganoderma sinense represent important and adjunctive therapeutic agents for treating various diseases, including leucopenia and hematopoietic injury. However, the synthetic accessibility to long, branched, and complicated carbohydrates chains from Ganoderma sinense polysaccharides remains a challenging task in chemical synthesis. Here, we report the modular chemical synthesis of nona-decasaccharide motif from Ganoderma sinense polysaccharide GSPB70-S with diverse biological activities for the first time through one-pot stereoselective glycosylation strategy on the basis of glycosyl ortho-(1-phenyvinyl)benzoates, which not only sped up carbohydrates synthesis but also reduced chemical waste and avoided aglycones transfer issues inherent to one-pot glycosylation on the basis of thioglycosides. The synthetic route also highlights the following key steps: (1) preactivation-based one-pot glycosylation for highly stereoselective constructions of several 1,2-cis-glycosidic linkages, including three α-d-GlcN-(1 → 4) linkages and one α-d-Gal-(1 → 4) bond via the reagent N-methyl-N-phenylformamide modulation; (2) orthogonal one-pot assembly of 1,2-trans-glycosidic linkages in various linear and branched glycans fragments by strategic combinations of glycosyl N-phenyltrifluoroacetimidates, glycosyl ortho-alkynylbenzoates, and glycosyl ortho-(1-phenyvinyl)benzoates; and (3) the final [1 × 4 + 15] Yu glycosylation for efficient assembly of nona-decasaccharide target. Additionally, shorter sequences of 4-mer, 5-mer, and 6-mer are also prepared for structure–activity relationship biological studies. The present work shows that this one-pot stereoselective glycosylation strategy can offer a reliable and effective means to streamline chemical synthesis of long, branched, and complex carbohydrates with many 1,2-cis-glycosidic bonds.

DOI: 10.1021/jacs.4c05188

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c05188