1-O-acetyl-2,3-di-O-benzoyl-5-deoxy-5-(diethoxyphosphinyl)-α-D-ribofuranose | 654075-03-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-O-acetyl-2,3-di-O-benzoyl-5-deoxy-5-(diethoxyphosphinyl)-α-D-ribofuranose
• 英文别名: diethyl [1-O-acetyl-2,3-di-O-benzoyl-5-deoxy-D-ribofuranos-5-C-yl]phosphonate；1-O-acetyl-5-deoxy-2,3-di-O-benzoyl-5-(diethoxyphosphinyl)-D-ribofuranose；1-O-Acetyl-2,3-di-O-benzoyl-5-deoxy-5-(diethoxyphosphinyl)-D-ribofuranose；[(2S,3S,4R)-5-acetyloxy-4-benzoyloxy-2-(diethoxyphosphorylmethyl)oxolan-3-yl] benzoate
• CAS: 654075-03-3
• 化学式: C₂₅H₂₉O₁₀P
• 分子量: 520.473
• InChiKey: ZOQBNTDIUBZBRJ-AEGADVIYSA-N

物化性质

• 沸点：
  617.6±55.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  36
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-O-acetyl-2,3-di-O-benzoyl-5-deoxy-5-(diethoxyphosphinyl)-α-D-ribofuranose 在 三氟甲磺酸三甲基硅酯 硫酸氢铵 、 三甲基溴硅烷 、 氨 、 六甲基二硅氮烷 作用下， 以 乙腈 为溶剂， 反应 48.0h， 生成 1-<5'-deoxy-5'-(dihydroxyphosphinyl)-β-D-ribofuranosyl>cytosine monoammonium salt
  参考文献：
  名称：

  Synthesis and biological properties of purine and pyrimidine 5'-deoxy-5'-(dihydroxyphosphinyl)-.beta.-D-ribofuranosyl analogs of AMP, GMP, IMP, and CMP

  摘要：

  Methyl 2,3-O-isopropylidene-D-ribofuranoside (1) was converted to 1-O-acetyl-5-bromo-5-deoxy-2,3-di-O-benzoyl-D-ribofuranose (6) in five steps with good yield. The Arbuzov condensation of compound 6 with triethyl phosphite resulted in the synthesis of 1-O-acetyl-2,3-di-O-benzoyl-5-deoxy-5-(diethoxyphosphinyl)-D-ribofuranos e (7). Compound 7 was used for direct glycosylation of both purine and pyrimidine bases. The glycosylation was accomplished with the dry silylated heterocyclic base in the presence of trimethylsilyl triflate. Deblocking of the glycosylation products gave exclusively the beta anomer of the 5'-phosphonate analogues of 9-[5'-deoxy-5'-(dihydroxyphosphinyl)-beta-D-ribofuranosyl]adenine (13), 9-[5'-deoxy-5'-(dihydroxyphosphinyl)-beta-D-ribofuranosyl]guanosin e (16), 9-[5'-deoxy-5'-(dihydroxyphosphinyl)-beta-D-ribofuranosyl]hypoxant hine (17), and 9-[5'-deoxy-5'-(dihydroxyphosphinyl)-beta-D-ribofuranosyl]cytosine (15), described here for the first time. The target compounds as well as their intermediates showed no in vitro antiviral or antitumor activity, although phosphorylation of 15 and 16 to di- and triphosphate analogues was demonstrated with use of isolated cellular enzymes.

  DOI：

  10.1021/jm00126a027
• 作为产物：
  描述：

  2,3-di-O-benzoyl-5-bromo-5-deoxy-D-ribofuranosyl acetate 、 亚磷酸三乙酯 在 乙醚 、 Brine 、 Sodium sulfate-III 、 Silica gel 、 乙酸乙酯 、 Hexanes 作用下， 反应 30.0h， 以Silica gel chromatography (EtOAc:Hexanes=80:20) yielded 59.4 g of the target compound (78%)的产率得到1-O-acetyl-2,3-di-O-benzoyl-5-deoxy-5-(diethoxyphosphinyl)-α-D-ribofuranose
  参考文献：
  名称：

  Antiviral phosphonate compounds and methods therefor

  摘要：

  药物组合物包括一种含有膦酸基团的核苷酸类似物，其浓度足以作为病毒聚合酶的底物和/或抑制剂，特别是对HCV RNA依赖性RNA聚合酶。

  公开号：

  US20040023921A1

文献信息

• Synthesis and Properties of ApA Analogues with Shortened Phosphonate Internucleotide Linkage
  作者：Šárka Králíková、Miloš Buděšínský、Ivan Barvík、Milena Masojídková、Zdeněk Točík、Ivan Rosenberg

  DOI：10.1080/15257770.2011.581259

  日期：2011.7

  complete series of the 2 ′–5 ′ and 3 ′–5 ′ regioisomeric types of r(ApA) and 2 ′-d(ApA) analogues with the α-hydroxy-phosphonate C3 ′-O-P-CH(OH)-C4 ″ internucleotide linkage, isopolar but non-isosteric with the phosphodiester one, were synthesized and their hybridization properties with polyU studied. Due to the chirality on the 5 ′-carbon atom of the modified internucleotide linkage bearing phosphorus

  具有α-羟基膦酸酯C3'-OP-CH（OH）-C4的r（ApA）和2'-d（ApA）类似物的2'-5'和3'-5'区域异构体的完整系列合成了与磷酸二酯同等但非等排的核苷酸间键，并研究了它们与polyU的杂交特性。由于具有磷和羟基部分的修饰的核苷酸间键的5'-碳原子上的手性，每个区域异构类型的ApA二聚体被拆分成差向异构对。为了检查α-羟基膦酸酯部分的5'-羟基在杂交过程中的作用，将合适的r（ApA）类似物与3'（2'）-OP-CH 2结合使用合成了缺乏5'-羟基的-C4''键。对修饰的糖-磷酸骨架的构象的核磁共振（NMR）光谱研究以及杂交测量表明，取决于5'-碳原子构型，与polyU的复合物的稳定性存在显着差异。讨论了α-羟基膦酸酯键在修饰的寡核糖核苷酸中的潜在用途。
• Synthesis of Azole Nucleoside 5′‐Monophosphate Mimics (P1Ms) and Their Inhibitory Properties of IMP Dehydrogenases
  作者：Guangyi Wang、Kandasamy Sakthivel、Vasanthakumar Rajappan、Thomas W. Bruice、Kathleen Tucker、Patrick Fagan、Jennifer L. Brooks、Tiffany Hurd、Janet M. Leeds、P. Dan Cook

  DOI：10.1081/ncn-120027838

  日期：2004.1.1

  IMPDH inhibitors have potential antimicrobial, anticancer and immunomodulatory effects. Nucleoside inhibitors of IMPDH exert their inhibitory effects via nucleoside 5'-MPs. Conversion of nucleoside analogs to NMPs by cellular nucleoside kinases is not assured, and usually is inefficient. In order to bypass cellular phosphorylation, a series of azole nucleoside 5'-MP mimics (P1Ms) based on ribavirin, EICAR and bredinin were synthesized and screened against human and C. albicans IMP dehydrogenises. P1Ms 8, 16, 25, 28 and 29 demonstrated substantial IMPDH inhibition with K-i values in low micromolar range.
• US7247621B2
  申请人：——

  公开号：US7247621B2

  公开（公告）日：2007-07-24