The Development of DNA-Compatible S-Glycosyl Transformations

In this study, we revealed two distinct S-glycosyl transformationsin a DNA-encoded library (DEL)-compatible environment. The first approachinvolves 2-chloro-1,3-dimethylimidazolidinium chloride (DMC)-mediatedS-glycosylation, which is facilitated by the coupling of unprotectedsugar units with the thiol residue of the DNA-linked compounds. However,this methodology falls short of the requirement for DEL constructiondue to its limited substrate scope. We further investigated a photoinducedDNA-compatible S-glycosyl transformation through a radical process.In this alternative approach, allyl sugar sulfones serve as sugardonors and are conjugated to DNA-linked compounds upon irradiationwith green light. Encouragingly, this on-DNA glycosyl chemistry demonstratedexcellent compatibility with functional groups presented in both sugarunits and peptides, affording the desired DNA-linked glycosyl derivativeswith good to excellent conversions. This pioneering DNA-compatibleS-glycosyl transformation represents a valuable tool, facilitatingthe preparation of glycosyl DELs and offering avenues for the explorationof sugar-incorporated delivery systems.

Automated summary

In this study, we discovered two different S-glycosyl transformations in a DNA-encoded library (DEL)-compatible environment. One approach involves 2-chloro-1,3-dimethylimidazolidinium chloride (DMC)-mediated S-glycosylation, but it has limited substrate scope for DEL construction. We also investigated a photoinduced DNA-compatible S-glycosyl transformation using allyl sugar sulfones, which showed excellent compatibility with functional groups and yielded desired DNA-linked glycosyl derivatives. This pioneering DNA-compatible S-glycosyl transformation is a valuable tool for preparing glycosyl DELs and exploring sugar-incorporated delivery systems.