Synthesis of α- And β-galactopyranose-configured isomers of cyclophellitol and cyclophellitol aziridine

Lianne I. Willems, Thomas J. M. Beenakker, Benjamin S. Murray, Berend Gagestein, Hans Van Den Elst, Erwin R. van Rijssel, Jeroen D C Codée, Wouter W. Kallemeijn, Johannes M F G Aerts, Gijsbert A. Van Der Marel, Herman S. Overkleeft*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Cyclophellitol and cyclophellitol aziridine are potent and irreversible mechanism-based inhibitors of retaining β-glucosidases. Alterations in the configuration of these compounds can lead to irreversible inhibition of different classes of retaining glycosidases. We have recently reported on the design of a set of α-galactopyranose-configured cyclophellitol and cyclophellitol aziridine derivatives that inhibit human retaining α-galactosidases. Moreover, we have shown that fluorescently labeled derivatives enable the activity-based profiling of these enzymes in vitro. In this report we describe in detail the synthetic strategies that were used to obtain these epoxide- and aziridine-based probes. In addition, we describe the parallel synthesis of a set of β-galactopyranose-configured cyclophellitol isomers as putative inhibitors of retaining β-galactosidases.

Original languageEnglish
Pages (from-to)6044-6056
Number of pages13
JournalEuropean Journal of Organic Chemistry
Issue number27
Publication statusPublished - 14 Aug 2014


  • Aziridines
  • Cyclitols
  • Enzyme inhibitors
  • Epoxides
  • Fluorescent probes
  • Irreversible inhibitors

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