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(4 H)-one} and (1' R)-spiro{1',5'-anhydro-d-glucitol-1',2-benzo[ b][1,4]thiazin-3(4 H)-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(4 H)-one} with the latter plant to show modest inhibition of germination (95% relative to control).
Keywords: ECD-TDDFT; anomeric spirocycle; benzo[][1,4]oxazinone; benzo[][1,4]thiazinone; glycogen phosphorylase; inhibition; plant germination; spiro-compound.