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Synthesis via a Carbohydrate‐Derived Münchnone of Pyrrolopyridines (Indolizines) and imidazopyridines, and their evaluation as inhibitors of β‐D‐glucosidases
Author(s) -
Granier Thierry,
Gaiser Florian,
Hintermann Lukas,
Vasella Andrea
Publication year - 1997
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19970800509
Subject(s) - chemistry , imidazole , cycloaddition , epimer , cyanide , glucosidases , stereochemistry , electrophile , silylation , cyanate , medicinal chemistry , organic chemistry , catalysis , hydrolysis
In the presence of activating agents, the N ‐acylglycine 8 reacts with electrophilic alkynes via the münchnone 9 to the pyrrolopyridines (= indolizines) 10, 18 , and 19 ( Scheme 1 ), Depending on the nature of the activating agent and the reaction temperature, the formation of the pyrroles was accompanied by partial epimerization to the manna ‐configurated epimers 16 and 17 . The gluco ‐configurated pyrrolopyridine 10 was deprotected to 12 . Silylation of 12 , followed by reduction and desilylation, gave the hexol 15 . Cycloaddition of 9 to 4‐toluenesulfonyl cyanide yielded 53% of the imidazole 23 , while cycloaddition to phenyl cyanate gave the phenoxyimidazole 28 in low yields only ( Scheme 2 ). As expected, the deprotected pyrroles 12, 15, 20 , and 21 are weak inhibitors of retaining β‐glucosidases, while the deprotected imidazole 24 derived from 23 proved a good inhibitor of sweet‐almond β‐glucosidases and a powerful inhibitor of Caldocellum saccharolyticum β‐glucosidase.