Organocatalysis Empowers Synthesis of Rare D‐ and L‐ glycero ‐L‐Heptopyranosyl Thioglycosides

作者：Xinxin Zhang, Chaomin Sun, Song Ni, Xin Tan, Xinfa Ding, Zhiwei Yu, Peng Wang, Xue‐Wei Liu, Peng Fu, Bin Lin, Ming Li · 发表于：Chinese Journal of Chemistry · 年份：2025 · DOI：10.1002/cjoc.70413 · 被引用次数：1 · 研究领域：Carbohydrate Chemistry and Synthesis、Glycosylation and Glycoproteins Research、Asymmetric Synthesis and Catalysis

Comprehensive Summary D‐ and L‐ glycero ‐L‐Heptopyranosyl residues are essential structural motifs in glycans and glycoconjugates, yet they remain challenging to obtain from natural sources. Herein, we disclose an efficient protocol for synthesizing D‐ and L‐ glycero ‐L‐heptopyranosyl thioglycosides, which are recognized as powerful glycosyl donors. Our strategy pivots on a C1‐to‐C5 switch strategy, commencing from readily accessible allyl α ‐ C ‐glycosides. The key transformations include a DBU‐catalyzed anomerization of easily available α ‐ C ‐glycosylethanals, an imidazolidinone‐catalyzed α ‐oxyamination of the aldehydes to install a chiral hydroxy group with high selectivity, and a decarboxylative transformation of the resulting uronic acids into the target thioglycosides. We found that the efficiency of the anomerization step is significantly influenced by the electronic nature of the protecting groups and the conformation of a sugar ring. Intriguingly, the stereoselectivity of the key oxyamination step was found to be independent of the catalyst's chirality. To demonstrate the practical application of this protocol, we synthesized three distinct thioglycosides, including 6‐ O ‐methyl‐D‐ glycero ‐L‐ gluco ‐heptopyranosyl thioglycoside, L‐ glycero ‐L‐ galacto ‐heptopyranosyl thioglycoside and L‐ glycero ‐L‐ manno ‐heptopyranosyl thioglycoside from the corresponding allyl α ‐ C ‐glycosides. The ready access to these glycosyl donors paves the way for synthesizing biological...