Modular Synthesis of Nucleoside Diphosphate Sugar Analogues Using Chlorosulfonyl Isocyanate and Dichlorophosphoryl Isocyanate

Organic Letters, vol. 28, pp. 912–916

Abstract

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.

Authors 9

1. Roy Steneker Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

2. Koen J. Rijpkema Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

3. Tim P. Ofman Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

4. Mert Sagiroglugil

   Universitat de Barcelona

   Affiliation as printed

   Departament de Química Inorgànica i Orgànica (Secció de Química Orgànica) and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Marti i Franques 1-11, E-08028 Barcelona, Spain

5. Carme Rovira

   Universitat de Barcelona

   Affiliation as printed

   Departament de Química Inorgànica i Orgànica (Secció de Química Orgànica) and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Marti i Franques 1-11, E-08028 Barcelona, Spain

6. Gijs A. van der MAREL Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

7. Dmitri V. Filippov Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

8. Herman S. Overkleeft corresponding Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

9. Jeroen D. C. Codée corresponding Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands