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Glucopyranosylidene-spiro-benzo[b][1,4]oxazinones and -benzo[b][1,4]thiazinones: Synthesis and Investigation of Their Effects on Glycogen Phosphorylase and Plant Growth Inhibition

Kun, Sándor, Kánya, Nándor, Galó, Norbert, Páhi, András, Mándi, Attila, Kurtán, Tibor, Makleit, Péter, Veres, Szilvia, Sipos, Ádám, Docsa, Tibor, Somsák, László
Journal of agricultural and food chemistry 2019 v.67 no.24 pp. 6884-6891
Lepidium sativum, Sinapis alba subsp. alba, circular dichroism spectroscopy, density functional theory, germination, glycogen, glycosides, glycosylation, growth retardation, hydrogenation, muscles, nitrophenols, nuclear magnetic resonance spectroscopy, organobromine compounds, phosphorylase, plant growth, pyridines, rabbits, temperature, transesterification, xylene
Glucopyranosylidene-spiro-benzo[b][1,4]oxazinones were obtained via the corresponding 2-nitrophenyl glycosides obtained by two methods: (a) AgOTf-promoted glycosylation of 2-nitrophenol derivatives by O-perbenzoylated methyl (α-d-gluculopyranosyl bromide)heptonate or (b) Mitsunobu-type reactions of O-perbenzoylated methyl (α-d-gluculopyranose)heptonate with bulky 2-nitrophenols in the presence of diethyl azodicarboxylate (DEAD) and PPh₃. Catalytic hydrogenation (H₂–Pd/C) or partial reduction (e.g., H₂–Pd/C, pyridine) of the 2-nitro groups led to spiro-benzo[b][1,4]oxazinones and spiro-benzo[b][1,4]-4-hydroxyoxazinones by spontaneous ring closure of the intermediate 2-aminophenyl or 2-hydroxylamino glycosides, respectively. The analogous 2-aminophenyl thioglycosides, prepared by reactions of O-perbenzoylated methyl (α-d-gluculopyranosyl bromide)heptonate with 2-aminothiophenols, were cyclized in m-xylene at reflux temperature to the corresponding spiro-benzo[b][1,4]thiazinones. O-Debenzoylation was effected by Zemplén transesterification in both series. Spiro-configurations were determined by NMR and electronic circular dichroism time-dependent density functional theory (ECD-TDDFT) methods. Inhibition assays with rabbit muscle glycogen phosphorylase b showed (1′R)-spiro{1′,5′-anhydro-d-glucitol-1′,2-benzo[b][1,4]oxazin-3(4H)-one} and (1′R)-spiro{1′,5′-anhydro-d-glucitol-1′,2-benzo[b][1,4]thiazin-3(4H)-one} to be the most efficient inhibitors (27 and 28% inhibition at 625 μM, respectively). Plant growth tests with white mustard and garden cress indicated no effect except for (1′R)-4-hydroxyspiro{1′,5′-anhydro-d-glucitol-1′,2-benzo[b][1,4]oxazin-3(4H)-one} with the latter plant to show modest inhibition of germination (95% relative to control).