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Minimally Protected and Stereoselective <i>O</i>-Glycosylation of Carboxylic Acid Allows Rapid Access to α-1-<i>O</i>- and 2-<i>O</i>-Acyl Glycosides

Bangxing Hao, Rongxia Li, Panpan Wang, Yingjie Wang, Xiaolong Li, Peng Xu, Qian Zhang, Xinhao Zhu, Xiaojuan Zhang, Yugen Zhu

2025Journal of the American Chemical Society11 citationsDOI

Abstract

We herein reported a catalytic, minimally protected, and highly α-stereoselective glycosylation protocol using carboxylic acid as an acceptor and glycosyl 8-alkynyl-1-naphthoate as a donor, enabling efficient access to unprotected α-1- O - and 2- O -acyl glycosides. This method demonstrates excellent functional compatibility and scope generality, allowing for the glycosylation of a wide range of complex carboxylic acids. Notably, we successfully synthesized two natural products, α-penta- O -galloyl- d -glucopyranose and nyctanthesin A, using this protocol. Mechanistic studies highlighted the crucial role of the 1- O ester functionality in ensuring chemoselectivity and the important contribution of the 2- O functionality in facilitating the reaction.

Topics & Concepts

ChemistryStereoselectivityGlycosylationGlycosideCarboxylic acidStereochemistryOrganic chemistryBiochemistryCatalysisCarbohydrate Chemistry and SynthesisGlycosylation and Glycoproteins ResearchChemical Synthesis and Analysis