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Synthesis of α‐ and β‐Galactopyranose‐Configured Isomers of Cyclophellitol and Cyclophellitol Aziridine
Author(s) -
Willems Lianne I.,
Beenakker Thomas J. M.,
Murray Benjamin,
Gagestein Berend,
van den Elst Hans,
van Rijssel Erwin R.,
Codée Jeroen D. C.,
Kallemeijn Wouter W.,
Aerts Johannes M. F. G.,
van der Marel Gijsbert A.,
Overkleeft Herman S.
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201402589
Subject(s) - aziridine , chemistry , stereochemistry , enzyme , combinatorial chemistry , in vitro , biochemistry , organic chemistry , ring (chemistry)
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.