Premium
Direct Stereoselective Aziridination of Cyclohexenols with 3‐Amino‐2‐(trifluoromethyl)quinazolin‐4(3 H )‐one in the Synthesis of Cyclitol Aziridine Glycosidase Inhibitors
Author(s) -
Artola Marta,
Wouters Shirley,
Schröder Sybrin P.,
de Boer Casper,
Chen Yurong,
Petracca Rita,
van den Nieuwendijk Adrianus M. C. H.,
Aerts Johannes M. F. G.,
van der Marel Gijsbert A.,
Codée Jeroen D. C.,
Overkleeft Herman S.
Publication year - 2019
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.201801703
Subject(s) - chemistry , aziridine , stereoselectivity , trifluoromethyl , steric effects , allylic rearrangement , glycoside hydrolase , stereochemistry , enantiopure drug , squaramide , stereoisomerism , enantioselective synthesis , combinatorial chemistry , organocatalysis , enzyme , organic chemistry , molecule , catalysis , ring (chemistry) , alkyl
Cyclophellitol aziridine and its configurational and functional isomers are powerful covalent inhibitors of retaining glycosidases, and find application in fundamental studies on glycosidases, amongst others in relation to inherited lysosomal storage disorders caused by glycosidase malfunctioning. Few direct and stereoselective aziridination methodologies are known for the synthesis of cyclophellitol aziridines. Herein, we present our studies on the scope of direct 3‐amino‐2‐(trifluoromethyl)quinazolin‐4(3 H )‐one‐mediated aziridination on a variety of configurational and functional cyclohexenol isosters. We demonstrate that the aziridination can be directed by an allylic or homoallylic hydroxyl through H‐bonding and that steric hindrance plays a key role in the diastereoselectivity of the reaction.