Premium
N ‐Thiocarbonyl Iminosugars: Synthesis and Evaluation of Castanospermine Analogues Bearing Oxazole‐2(3 H )‐thione Moieties
Author(s) -
Silva Sandrina,
SánchezFernández Elena M.,
Ortiz Mellet Carmen,
Tatibouët Arnaud,
Pilar Rauter Amélia,
Rollin Patrick
Publication year - 2013
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.201300720
Subject(s) - chemistry , oxazole , moiety , stereochemistry , nucleophile , intramolecular force , oxazoline , castanospermine , oxazolidine , combinatorial chemistry , organic chemistry , enzyme , catalysis
A straightforward and efficient synthetic route to a new class of glycosidase inhibitors containing an oxazole‐2(3 H )‐thione moiety has been devised. The approach involves the formation of α‐hydroxy ketones, which, after condensation with thiocyanic acid, leads to the formation of the heterocycle. By exploiting the ability of the nitrogen atom of oxazoline‐2‐thione precursors to act as nucleophiles in intramolecular addition, castanospermine analogues could be readily prepared in good overall yields. Glycosidase inhibitory activity compared to oxazolidinethione analogues showed a strong influence of the double bond, for example with pseudoiminosugar 19 , by suppressing α‐glucosidase inhibition and introducing, to a moderate level, β‐glucosidase inhibitory activity. Reactivities showed the propensity of oxazole‐2(3 H )‐thiones – especially when fused on carbohydrate frames – to convert into 1,3‐oxazolidine‐2‐thione aminals through nucleophilic addition to the double bond, leading to unexpected tricyclic structure 21 .