Modular synthesis of nucleoside diphosphate sugar analogues using chlorosulfonyl isocyanate and dichlorophosphoryl isocyanate

Steneker, R.; Rijpkema, K.J.; Ofman, T.P.; Sagiroglugil, M.; Rovira, C.; Marel, G.A. van der; ... ; Codée, J.D.C. (2026)

Article / Letter to editor

Pyrophosphates are central to biology, and synthetic pyrophosphate isosteres are widely sought to create biomimetic molecules to study diverse biochemical processes. We describe a flexible, modular synthesis of nucleoside diphosphate sugar analogues by linking carbasugars and nucleosides with the dual electrophilic reagents chlorosulfonyl isocyanate and dichlorophosphoryl isocyanate, introducing sulfonyl- and phosphoryl-carbamate linkages as pyrophosphate isosteres, respectively. The resulting GDP-fucose and UDP-GlcNAc analogues may inhibit glycosyltransferases and serve as tools for studying pyrophosphate-processing enzymes.

• All authors: Steneker, R.; Rijpkema, K.J.; Ofman, T.P.; Sagiroglugil, M.; Rovira, C.; Marel, G.A. van der; Filippov, D.V.; Overkleeft, H.S.; Codée, J.D.C.
• Date: 2026-01-13
• Journal: Organic Letters
• Volume: 28
• Issue: 3
• Pages: 912 - 916
• DOI: doi:10.1021/acs.orglett.5c04568
• Link: https://pubs.acs.org/doi/10.1021/acs.orglett.5c04568