Zhao Qingyi, Bao Yandan, Niu Dawen, Wang Xuan, Lu Xiaojie
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai, 201203, China.
Org Lett. 2023 Jul 7;25(26):4940-4944. doi: 10.1021/acs.orglett.3c01799. Epub 2023 Jun 26.
In this study, we revealed two distinct S-glycosyl transformations in a DNA-encoded library (DEL)-compatible environment. The first approach involves 2-chloro-1,3-dimethylimidazolidinium chloride (DMC)-mediated S-glycosylation, which is facilitated by the coupling of unprotected sugar units with the thiol residue of the DNA-linked compounds. However, this methodology falls short of the requirement for DEL construction due to its limited substrate scope. We further investigated a photoinduced DNA-compatible S-glycosyl transformation through a radical process. In this alternative approach, allyl sugar sulfones serve as sugar donors and are conjugated to DNA-linked compounds upon irradiation with green light. Encouragingly, this on-DNA glycosyl chemistry demonstrated excellent compatibility with functional groups presented in both sugar units and peptides, affording the desired DNA-linked glycosyl derivatives with good to excellent conversions. This pioneering DNA-compatible S-glycosyl transformation represents a valuable tool, facilitating the preparation of glycosyl DELs and offering avenues for the exploration of sugar-incorporated delivery systems.
在本研究中，我们在与DNA编码文库（DEL）兼容的环境中揭示了两种不同的S-糖基转化。第一种方法涉及2-氯-1,3-二甲基咪唑啉鎓氯化物（DMC）介导的S-糖基化，其通过未保护的糖单元与DNA连接化合物的硫醇残基偶联来实现。然而，由于其有限的底物范围，该方法不符合DEL构建的要求。我们进一步研究了通过自由基过程进行的光诱导DNA兼容的S-糖基转化。在这种替代方法中，烯丙基糖砜用作糖供体，并在绿光照射下与DNA连接化合物共轭。令人鼓舞的是，这种基于DNA的糖基化学与糖单元和肽中存在的官能团表现出优异的兼容性，以良好至优异的转化率提供所需的DNA连接的糖基衍生物。这种开创性的DNA兼容S-糖基转化代表了一种有价值的工具，有助于糖基DEL的制备，并为探索含糖递送系统提供了途径。
