Chien Tun-Cheng, Berry David A, Drach John C, Townsend Leroy B
Department of Chemistry, College of Literature, Science and Arts, The University of Michigan, Ann Arbor, Michigan 48109-1065, USA.
Nucleosides Nucleotides Nucleic Acids. 2005;24(10-12):1971-96. doi: 10.1080/15257770500269531.
3-Amino-6-(beta-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) was synthesized via an N-N bond formation strategy by a mononuclear heterocyclic rearrangement (MHR). A series of 5-amino-1-(5-O-tert-butyldimethylsilysilyl-2,3-O-isopropylidene-beta-D-ribofuranosyl)-4-(1,2,4-oxadiazol-3-yl)imidazoles (6a-d), with different substituents at the 5-position of the 1,2,4-oxadiazole, were synthesized from 5-amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxamide (AICA Ribose, 3). It was found that 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-beta-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) (7b and/or 7a) 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-(beta-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) as a 5:5 fused analog of adenosine (1).
3-氨基-6-(β-D-呋喃核糖基)咪唑并[4,5-c]吡唑(2)通过单核杂环重排(MHR)的N-N键形成策略合成。由5-氨基-1-(β-D-呋喃核糖基)咪唑-4-甲酰胺(AICA核糖,3)合成了一系列在1,2,4-恶二唑5位具有不同取代基的5-氨基-1-(5-O-叔丁基二甲基硅烷基-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(6a-d)。发现5-氨基-1-(5-O-叔丁基二甲基硅烷基-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中与氢化钠进行MHR，以良好的产率得到相应的3-乙酰氨基咪唑并[4,5-c]吡唑核苷(7b和/或7a)。在许多条件下直接从3-乙酰氨基咪唑并[4,5-c]吡唑上去除乙酰基均未成功。随后的保护基操作得到了所需的3-氨基-6-(β-D-呋喃核糖基)咪唑并[4,5-c]吡唑(2)，它是腺苷(1)的5:5稠合类似物。
