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In Search of Glycogen Phosphorylase Inhibitors: 5‐Substituted 3‐ C ‐Glucopyranosyl‐1,2,4‐oxadiazoles from β‐ D ‐Glucopyranosyl Cyanides upon Cyclization of O ‐Acylamidoxime Intermediates
Author(s) -
Benltifa Mahmoud,
Vidal Sébastien,
Fenet Bernard,
Msaddek Moncef,
Goekjian Peter G.,
Praly JeanPierre,
Brunyánszki Attila,
Docsa Tibor,
Gergely Pál
Publication year - 2006
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.200600073
Subject(s) - chemistry , hydroxylamine , glycogen phosphorylase , acylation , glycogen , organic chemistry , stereochemistry , biochemistry , catalysis
Abstract Upon treatment with hydroxylamine‐, benzyl‐ and benzoyl‐protected β‐ D ‐glucopyranosyl cyanides efficiently afforded the corresponding amidoximes. They reacted by O ‐acylation in the presence of carboxylic acids or acyl chlorides to provide benzyl‐ and benzoyl‐protected O ‐acylamidoximes. The latter were isolated and fully characterized. Thermal cyclization of O ‐acylamidoximes yielded the corresponding 5‐substituted 3‐ C ‐β‐ D ‐glucopyranosyl‐1,2,4‐oxadiazoles, either in a “one‐pot” procedure (benzylated series), or in two steps (benzoylated series). The twelve 5‐substituted 1,2,4‐oxadiazoles obtained upon debenzoylation were assayed against glycogen phosphorylase (GP). 3‐ C ‐(β‐ D ‐Glucopyranosyl)‐5‐(2‐naphthyl)‐1,2,4‐oxadiazole was the best inhibitor of rabbit muscle glycogen phosphorylase b ( K i = 38.4 ±3.0 μ M ). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)