SYNTHESIS OF 6-METHOXY-2(1H)-PYRIDINONE AND 6-CHLORO-2(1H)-PYRIDINONE ACYCLO-C-NUCLEOSIDES FROM 2H-1,4-OXAZIN-2-ONES

Starting from 6-variated 3-methoxy- and 3-chloro-2H-1,4-oxazin-2-ones 4a-e the synthesis of a series of 6-methoxy- and 6-chloro-2(1H)-pyridinone acyclo-C-nucleosides 2a-d and 3a-d was accomplished. Diels-Alder reaction of the oxazinones 4a-e with propargyl bromide yielded the corresponding 3-bromomethylpyridines Sa-e, which underwent easy substitution of the bromine atom with the appropriate nucleophiles, permitting the introduction of acyclo sugar moieties. Further treatment with sodium phenylmethoxide in dry dimethylformamide afforded the benzyl protected C-nucleosides 8a-d and 9a-d. Debenzylation of 8a-d in ethanol using a palladium-carbon catalyst poisoned with strontium carbonate and deprotection of 9a-d with boron trichloride at - 78-degrees-C provided stable 6-methoxy- and 6-chloro-2(1H)-pyridinone acyclo-C-nucleosides 2a-d and 3a-d respectively.