Synthesis of new N-substituted 3,4,5-trihydroxypiperidin-2-ones from d-ribono-1,4-lactone

d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d-ribonamide 8a in quantitative yield. Using this reaction procedure, N-butyl, N-hexyl, N-dodecyl, N-benzyl, N-(3-methyl-pyridinyl)-, N-(2-hydroxy-ethyl)-, and N-(2-cyano-ethyl)-d-ribonamides 8b-h were obtained in quantitative yield. Bromination of the amides 8a-e with acetyl bromide in dioxane followed by acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxy-N-ethyl, N-butyl, N-hexyl, N-dodecyl, and N-benzyl-d-ribonamides 9a-e in 40-54% yields. To obtain 2,3,4-tri-O-acetyl-5-bromo-5-deoxy-N-(3-methyl-pyridinyl)-, N-(2-hydroxy-ethyl)-, and N-(2-cyano-ethyl)-9f-h, the bromination is necessary before the amidation reaction. Treatment of the bromoamides 9a-h with NaH in DMF followed by methanolysis affords N-alkyl-d-ribono-1,5-lactams 12a-h in quantitative yield.