Photolabile fluorous tag-assisted synthesis of type I and type II oligofucosides and their derivatives

Fucoidan has attracted attention due to its broad range of biological activities, but the heterogeneity of extracted fucoidan limits in-depth understanding of its structure-activity relationships. In this study, we developed an efficient synthetic strategy for type I and type II oligofucosides using a photolabile fluorous tag. A concise route for the synthesis of the photolabile fluorous tag was explored (from vanillin in four steps, 67% overall yield). Then, type I (α-1,3-linked) and type II (alternating α-1,3- and α-1,4-linked) oligofucosides were rapidly assembled by polytetrafluoroethylene (PTFE)-assisted purification, providing fucose octasaccharides in ∼50% overall yield over six steps, with an average >89% yield per step. Finally, photocleavage of the fluorous tag allowed the resultant glycans to be converted to glycosyl donors, enabling rapid reducing-end modification with dihydrocholesterol in high yield. The efficient approach established in this work enables access to structurally well-defined oligofucosides, thus laying a solid material foundation for subsequent derivatization and systematic structure-activity relationship studies.