从 D-核糖-1,4-内酯合成新型 N-取代的 3,4,5-三羟基哌啶-2-酮。

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

机构信息

Laboratoire des Glucides, UMR 6219, Université de Picardie Jules Verne, 33 Rue Saint-Leu, F-80039 Amiens, France.

出版信息

Carbohydr Res. 2010 Sep 23;345(14):1983-7. doi: 10.1016/j.carres.2010.07.005. Epub 2010 Aug 6.

DOI:10.1016/j.carres.2010.07.005

PMID:20692650

Abstract

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.

摘要

d-核糖-1,4-内酯与乙胺在 DMF 中反应，定量得到 N-乙基-d-核糖酰胺 8a。使用该反应程序，定量得到 N-丁基、N-己基、N-十二烷基、N-苄基、N-(3-甲基吡啶基）、N-(2-羟乙基）和 N-(2-氰乙基）-d-核糖酰胺 8b-h。酰胺 8a-e 与乙酰溴在二氧六环中溴化，然后乙酰化，得到 2,3,4-三-O-乙酰基-5-溴-5-脱氧-N-乙基、N-丁基、N-己基、N-十二烷基和 N-苄基-d-核糖酰胺 9a-e，产率为 40-54%。为了得到 2,3,4-三-O-乙酰基-5-溴-5-脱氧-N-(3-甲基吡啶基）、N-(2-羟乙基）和 N-(2-氰乙基）-9f-h，需要在酰胺化反应之前进行溴化反应。溴代酰胺 9a-h 与 DMF 中的 NaH 反应，然后甲醇解，定量得到 N-烷基-d-核糖-1,5-内酰胺 12a-h。