TY - JOUR
T1 - Synthesis of α- And β-galactopyranose-configured isomers of cyclophellitol and cyclophellitol aziridine
AU - Willems, Lianne I.
AU - Beenakker, Thomas J. M.
AU - Murray, Benjamin S.
AU - Gagestein, Berend
AU - Van Den Elst, Hans
AU - Rijssel, Erwin R. van
AU - Codée, Jeroen D C
AU - Kallemeijn, Wouter W.
AU - Aerts, Johannes M F G
AU - Van Der Marel, Gijsbert A.
AU - Overkleeft, Herman S.
PY - 2014/8/14
Y1 - 2014/8/14
N2 - 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.
AB - 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.
KW - Aziridines
KW - Cyclitols
KW - Enzyme inhibitors
KW - Epoxides
KW - Fluorescent probes
KW - Irreversible inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85027922785&partnerID=8YFLogxK
U2 - 10.1002/ejoc.201402589
DO - 10.1002/ejoc.201402589
M3 - Article
AN - SCOPUS:85027922785
VL - 2014
SP - 6044
EP - 6056
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
SN - 1434-193X
IS - 27
ER -