Synthesis of 3-aminoimidazo[4,5-c]pyrazole nucleoside via the N-N bond formation strategy as a [5:5] fused analog of adenosine.
Synthesis of 3-aminoimidazo[4,5-c]pyrazole nucleoside via the N-N bond formation strategy as a [5:5] fused analog of adenosine.
复制标题
通过 N-N 键形成策略合成 3-氨基咪唑并[4,5-c]吡唑核苷作为腺苷的 [5:5] 融合类似物。
DOI：
10.1080/15257770500269531
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Townsend,LeroyB
中科院分区：
文献类型：
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作者：
Chien,Tun-Cheng;Berry,DavidA;Drach,JohnC;Townsend,LeroyB
通过单核杂环重排（MHR），采用N-N键形成策略合成了3-氨基-6-（β-D-呋喃核糖基）咪唑并[4，5-c]吡唑（2）。以5-氨基-1-（β-D-呋喃核糖基）咪唑-4-甲酰胺（AICA Ribose，3）为起始原料，合成了一系列5-氨基-1-（5-O-叔丁基二甲基硅基-2，3-O-异亚丙基-β-D-呋喃核糖基）-4-（1，2，4-恶二唑-3-基）咪唑啉（6a-d）。发现5-氨基-1-（5-O-叔丁基二甲基硅基-2，3-O-异亚丙基-β-D-呋喃核糖基）-4-（5-甲基-1，2，4-恶二唑-3-基）咪唑（6a）在DMF或DMSO中与氢化钠反应，以良好的产率得到相应的3-乙酰胺基咪唑并[4，5-c]吡唑核苷（7带/或7a）。在许多条件下，从3-乙酰氨基咪唑并[4，5-c]吡唑中直接除去乙酰基是不成功的。随后的保护基团操作得到所需的3-氨基-6-（β-D-呋喃核糖基）咪唑并[4，5-c]吡唑（2），其为腺苷（1）的5：5融合类似物。
3-Amino-6-(β-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) was synthesized via anN-Nbond formation strategy by a mononuclear heterocyclic rearrangement (MHR). A series of 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D-ribofuranosyl-4-(1,2,4-oxadiazol-3-yl)imidaz-oles (6a-d), with different substituents at the 5-position of the 1,2,4-oxadiazole, were synthesized from 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (AICA Ribose,3). It was found that 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D-ribofuranosyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)imidazole (6a) underwent the MHR with sodium hydride in DMF or DMSO to afford the corresponding 3-acetamidoimidazo[4,5-c]pyrazole nucleoside(s) (7band/or7a) in good yields. A direct removal of the acetyl group from 3-acetamidoimidazo[4,5-c]pyrazoles under numerous conditions was unsuccessful. Subsequent protecting group manipulations afforded the desired 3-amino-6-(β-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) as a 5:5 fused analog of adenosine (1).