[(2S,5R)-5-(2-氨基-6-溴嘌呤-9-基)四氢呋喃-2-基]甲醇 | 132194-22-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: [(2S,5R)-5-(2-氨基-6-溴嘌呤-9-基)四氢呋喃-2-基]甲醇
• 英文名称: 2-amino-6-bromo-9-(2,3-dideoxy-β-D-glycero-pentofuranosyl)-9H-purine
• 英文别名: 2-Amino-6-bromo-9-(2,3-dideoxy-β-D-glycero-pentofuranosyl)purine；2-Amino-6-bromo-9-(2,3-dideoxy-beta-D-glycero-pentofuranosyl)-9H-purine；[(2S,5R)-5-(2-amino-6-bromopurin-9-yl)oxolan-2-yl]methanol
• CAS: 132194-22-0
• 化学式: C₁₀H₁₂BrN₅O₂
• 分子量: 314.142
• InChiKey: WXINSBSCFDVBBO-NTSWFWBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-6-溴嘌呤 、 2',3'-二脱氧尿苷 反应 3.0h， 以21.3%的产率得到[(2S,5R)-5-(2-氨基-6-溴嘌呤-9-基)四氢呋喃-2-基]甲醇
  参考文献：
  名称：

  Escherichia coli mediated biosynthesis and in vitro anti-HIV activity of lipophilic 6-halo-2',3'-dideoxypurine nucleosides

  摘要：

  A series of 6-substituted 2',3'-dideoxypurine ribofuranosides (ddP) was enzymatically synthesized with live E. coli in an effort to enhance the lipophilicity of this class of anti-human immunodeficiency virus (HIV) compounds and thereby facilitate drug delivery into the central nervous system. All 6-halo-substituted ddPs were substantially more lipophilic, as defined by their octanol-water partition coefficient (P), than their nonhalogenated congeners 2',3'-dideoxyinosine (ddI) or 2',3'-dideoxyguanosine (ddG). For this class of compounds, log P's ranged from +0.5 to -1.2 in the following order: 6-iodo, 2-amino-6-iodo > 6-bromo, 2-amino-6-bromo > 6-chloro, 2-amino-6-chloro > 6-fluoro, 2-amino-6-fluoro >> ddG > ddI. These compounds were evaluated in vitro for ability to suppress the infectivity, replication, and cytopathic effect of HIV. 2-Amino-6-fluoro-, 2-amino-6-chloro-, and 6-fluoro-ddP exhibited a potent activity against HIV comparable to that of ddI or ddG and completely blocked the infectivity of HIV without affecting the growth of target cells. The comparative order of in vitro anti-HIV activity was 2-amino-6-fluoro, 2-amino-6-chloro, 6-fluoro > 2-amino-6-bromo > 2-amino-6-iodo, 6-chloro > 6-bromo > 6-iodo. These compounds also exhibited potent in vitro activity against HIV-2 and 3'-azido-3'-deoxythymidine-resistant HIV-1 variants. All 2-amino-6-halo-ddPs and 6-halo-ddPs were substrates for adenosine deaminase (ADA) and were converted to ddG or ddI, respectively. In the presence of the potent ADA inhibitor 2'-deoxycoformycin, 6-halo-substituted ddPs failed to exert an in vitro antiretroviral effect. These dideoxypurine nucleoside analogues represent a new class of lipophilic prodrugs of ddG and ddI that possess the potential for more effective therapy of HIV-induced neurologic disorders.

  DOI：

  10.1021/jm00109a012

文献信息

• Nucleic Acid-Related Compounds. 88. Efficient Conversions of Ribonucleosides into Their 2',3'-Anhydro, 2'(and 3')-Deoxy, 2',3'-Didehydro-2',3'-dideoxy, and 2',3'-Dideoxynucleoside Analogs
  作者：Morris J. Robins、John S. Wilson、Danuta Madej、Nicholas H. Low、Fritz Hansske、Stanislaw F. Wnuk

  DOI：10.1021/jo00129a034

  日期：1995.12

  Treatment of purine, pyrimidine, and modified purine (antibiotic) ribonucleosides with 2-acetoxy-2-methylpropanoyl (alpha-acetoxyisobutyryl) bromide in acetonitrile gave mixtures of 2',3'-bromohydrin acetates with different O5' substituents. Significant amounts of 5'-unprotected (hydroxyl) bromo acetates were obtained in some cases, and formation of 2',3'-O-isopropylidene derivatives as minor byproducts was detected for the first time. Acid-catalyzed nucleophilic displacement of chloride by bromide occurred with 2-amino-6-chloropurine riboside, but no substitution of fluoride by bromide was detected with 6-amino-2-fluoropurine riboside. Treatment of the trans bromo acetate mixtures obtained from purine-type nucleosides with Dowex 1 x 2 (OH-) in methanol gave the 2',3'-anhydro (ribo epoxide) compounds. Radical-mediated hydrogenolytic debromination and deprotection gave 2'- and 3'-deoxynucleosides. Treatment of the bromo acetate mixtures with zinc-copper couple or acetic acid-activated zinc effected reductive elimination, and deprotection gave 2',3'-didehydro-2',3'-dideoxy compounds which were hydrogenated to give 2',3'-dideoxynucleosides. A number of these analogues have potent inhibitory activity against AIDS and hepatitis B viruses. New C-13 NMR data for several types of unsaturated-sugar nucleosides are tabulated. These procedures are directly applicable for the preparation of L-didehydro-dideoxy and L-dideoxy nucleoside analogues.
• MURAKAMI, KUNICHIKA;SHIRASAKA, TAKUMA;YOSHIOKA, HIDETOSHI;KOJIMA, EIJI;AO+, J. MED. CHEM., 34,(1991) N, C. 1606-1612
  作者：MURAKAMI, KUNICHIKA、SHIRASAKA, TAKUMA、YOSHIOKA, HIDETOSHI、KOJIMA, EIJI、AO+

  DOI：——

  日期：——
• Escherichia coli mediated biosynthesis and in vitro anti-HIV activity of lipophilic 6-halo-2',3'-dideoxypurine nucleosides
  作者：Kunichika Murakami、Takuma Shirasaka、Hidetoshi Yoshioka、Eiji Kojima、Shizuko Aoki、Harry Ford、John S. Driscoll、James A. Kelley、Hiroaki Mitsuya

  DOI：10.1021/jm00109a012

  日期：1991.5

  A series of 6-substituted 2',3'-dideoxypurine ribofuranosides (ddP) was enzymatically synthesized with live E. coli in an effort to enhance the lipophilicity of this class of anti-human immunodeficiency virus (HIV) compounds and thereby facilitate drug delivery into the central nervous system. All 6-halo-substituted ddPs were substantially more lipophilic, as defined by their octanol-water partition coefficient (P), than their nonhalogenated congeners 2',3'-dideoxyinosine (ddI) or 2',3'-dideoxyguanosine (ddG). For this class of compounds, log P's ranged from +0.5 to -1.2 in the following order: 6-iodo, 2-amino-6-iodo > 6-bromo, 2-amino-6-bromo > 6-chloro, 2-amino-6-chloro > 6-fluoro, 2-amino-6-fluoro >> ddG > ddI. These compounds were evaluated in vitro for ability to suppress the infectivity, replication, and cytopathic effect of HIV. 2-Amino-6-fluoro-, 2-amino-6-chloro-, and 6-fluoro-ddP exhibited a potent activity against HIV comparable to that of ddI or ddG and completely blocked the infectivity of HIV without affecting the growth of target cells. The comparative order of in vitro anti-HIV activity was 2-amino-6-fluoro, 2-amino-6-chloro, 6-fluoro > 2-amino-6-bromo > 2-amino-6-iodo, 6-chloro > 6-bromo > 6-iodo. These compounds also exhibited potent in vitro activity against HIV-2 and 3'-azido-3'-deoxythymidine-resistant HIV-1 variants. All 2-amino-6-halo-ddPs and 6-halo-ddPs were substrates for adenosine deaminase (ADA) and were converted to ddG or ddI, respectively. In the presence of the potent ADA inhibitor 2'-deoxycoformycin, 6-halo-substituted ddPs failed to exert an in vitro antiretroviral effect. These dideoxypurine nucleoside analogues represent a new class of lipophilic prodrugs of ddG and ddI that possess the potential for more effective therapy of HIV-induced neurologic disorders.