Linkage-Editing of β-Glucosylceramide and β-Glucosylcholesterol: Development of β-Selective C -Glucosylation and Potent Mincle Ligands

Suzuka Chiba; Wakana Kusuhara; Eri Ishikawa; Makoto Yoritate; Taishi Miura; Kazushi Maeda; Haruto Takamura; Hiroaki Matoba; Sho Yamasaki; Go Hirai

doi:10.1021/jacs.5c17740

Linkage-Editing of β-Glucosylceramide and β-Glucosylcholesterol: Development of β-Selective C -Glucosylation and Potent Mincle Ligands

Journal of the American Chemical Society 2026

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Authors: Suzuka Chiba, Wakana Kusuhara, Eri Ishikawa, Makoto Yoritate, Taishi Miura, Kazushi Maeda, Haruto Takamura, Hiroaki Matoba, Sho Yamasaki, Go Hirai

DOI: 10.1021/jacs.5c17740

Cited by: 14

References: 62

Abstract

Despite recent advances, highly stereoselective C -glucosylation for the synthesis of glycan analogs with diverse C -glycoside linkages (linkage-edited pseudoglycans) remains a considerable challenge. Here, we present a β-selective C -glucosylation method using a 2,4-bis(triisopropylsilyl)-protected glucosyl bromide donor. Direct coupling with ceramide and cholesterol-derived bromofluoroolefins provides access to analogs of β-glucosylceramide (pseudo-β-GlcCer) and β-glucosylcholesterol (pseudo-β-GlcChol) containing CH 2 -, ( R )–CHF-, and ( S )–CHF-linkages. Pseudo-β-GlcCers activated immune responses in mouse bone marrow-derived macrophages and dendritic cells more potently than native β-GlcCer, with distinct immune activity patterns, depending on the linkage type.

Fields of Study & Subjects

Carbohydrate Chemistry and Synthesis Glycosylation and Glycoproteins Research Sphingolipid Metabolism and Signaling

Publication details

Journal / source: Journal of the American Chemical Society
Publisher: American Chemical Society (ACS)
Volume: 148
Issue: 3
Pages: 3316–3326
Publication date: 10 January 2026
Language: EN

References 62