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).

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A systematic study was performed by using Mitsunobu conditions (diethyl azodicarboxylate, Ph3P or n-Bu3P in THF or CH3CN) for glycosylations with methyl 3,4,5,7-tetra-O-benzoyl-α-D-gluco-hept-2-ulopyranosonate. From a set of 47 O-, N-,...

Glycosylidene-spiro-morpholin(on)es are scarcely described skeletons in the literature. In this work, we have systematically explored the synthetic routes towards such morpholinones based on the reactions of O-peracylated hept-2-ulopyranosonamide derivatives of D-gluco and D-galacto configuration. Koenigs–Knorr type glycosylation of 2-chloroethanol, allylic and propargylic alcohols by (glyculosylbromide)onamides furnished the expected glycosides. The 2-chloroethyl glycosides were ring closed to the corresponding spiro-morpholinones by treatment with K2CO3. The (allyl glyculosid)onamides gave diastereomeric mixtures of spiro-5-hydroxymorpholinones by ozonolysis and 5-iodomethylmorpholinones under iodonium ion mediated conditions. The ozonolytic method has not yet been known for the construction of morpholine rings, therefore, it was also extended to O-allyl mandelamide. The 5-hydroxymorpholinones were subjected to oxidation and acid catalyzed elimination reactions to give the corresponding morpholine-3,5-dions and 5,6-didehydro-morpholin-3-ones, respectively. Base induced elimination of the 5-iodomethylmorpholinones gave 5-methyl-2H-1,4-oxazin-3(4H)-ones. O-Acyl protecting groups of all of the above compounds were removed under Zemplén conditions. Some of the D-gluco configured unprotected compounds were tested as inhibitors of glycogen phosphorylase, but showed no significant effect.

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