<i>Para</i>-(3-phenylpropiolamido)phenyl (PPAP) glycosides: Harnessing <i>ipso</i>-cyclization-driven glycosylation for strategic flexibility.

Abstract

We herein report <i>para</i>-(3-phenylpropiolamido)phenyl (PPAP) glycosides as a novel class of glycosyl donors with distinct advantages for carbohydrate synthesis. These donors, featured by an intrinsically stable phenolic linkage, undergo glycosylation via a unique <i>ipso</i>-cyclization-mediated activation. Activated with <i>N</i>-iodosuccinimide (NIS)/trimethylsilyl trifluoromethanesulfonate (TMSOTf), PPAP donors support both O- and N-glycosylation across a broad range of substrates. Guided by density functional theory calculations, their design allows straightforward synthesis through a simple amide coupling reaction, facilitating diverse latent-active transformations and broadening their strategic utility. Furthermore, the distinct reactivity profile of PPAP donors-marked by a clear gap relative to other known donors and orthogonality to many standard activation methods-makes them well suited for modular, one-pot glycosylation strategies. Their ease of synthesis, robust performance in glycosylation, and compatibility with diverse assembly approaches collectively establish PPAP glycosides as powerful tools for the efficient construction of complex carbohydrates.