9-[5-O-(tert-butyldimethylsilyl)-2-deoxy-2-fluoro-3-O-(phenoxythiocarbonyl)-β-D-arabinofuranosyl]adenine | 125542-17-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 9-[5-O-(tert-butyldimethylsilyl)-2-deoxy-2-fluoro-3-O-(phenoxythiocarbonyl)-β-D-arabinofuranosyl]adenine
• 英文别名: [(2R,3R,4S,5R)-5-(6-aminopurin-9-yl)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-fluorooxolan-3-yl]oxy-phenoxymethanethione
• CAS: 125542-17-8
• 化学式: C₂₃H₃₀FN₅O₄SSi
• 分子量: 519.672
• InChiKey: FTKBEDYKZIENMR-VWFIUDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.41
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  9-[5-O-(tert-butyldimethylsilyl)-2-deoxy-2-fluoro-3-O-(phenoxythiocarbonyl)-β-D-arabinofuranosyl]adenine 在 偶氮二异丁腈 、 四丁基氟化铵 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 0.68h， 生成 2'-beta-氟-2',3'-二脱氧腺苷
  参考文献：
  名称：

  Acid-stable 2'-fluoro purine dideoxynucleosides as active agents against HIV

  摘要：

  2',3'-Dideoxy purine nucleosides have anti-HIV activity in vitro and the inosine analogue is being clinically evaluated. The instability of these compounds toward acidic conditions complicates oral administration. The effect of the addition of a fluorine atom to the 2'-position was investigated by preparing the fluorine-containing 2'-erythro and 2'-threo isomers of ddA and the threo isomer of ddI. All fluorine-containing compounds were indefinitely stable to acidic conditions which completely decomposed ddI (1) and ddA (2) in minutes. While the fluorine-containing erythro isomer, 5, was inactive, the threo isomers, 2'-F-dd-ara-A (3) and 2'-F-dd-ara-I (4), were just as potent and active in protecting CD4+ ATH8 cells from the cytopathogenic effects of HIV-1 as the parent drugs. Exposure to pH 1 at 37 degrees C prior to testing destroyed the activity of ddA and ddI but left the anti-HIV properties of 3 and 4 unchanged. The fluorinated analogues also protected cells exposed to HIV-2 and inhibited gag gene product expression but not as effectively as the parent compounds. The fluorine-containing analogues appear to be somewhat more toxic in vitro to the antigen- and mitogen-driven proliferation of immunocompetent cells than their corresponding parent compounds.

  DOI：

  10.1021/jm00165a015
• 作为产物：
  描述：

  1,3-di-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranose 在 咪唑 、 (dimethylamido)pyridine 、 4 A molecular sieve 、 氨 、 氢溴酸 作用下， 以 甲醇 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 101.5h， 生成 9-[5-O-(tert-butyldimethylsilyl)-2-deoxy-2-fluoro-3-O-(phenoxythiocarbonyl)-β-D-arabinofuranosyl]adenine
  参考文献：
  名称：

  Acid-stable 2'-fluoro purine dideoxynucleosides as active agents against HIV

  摘要：

  2',3'-Dideoxy purine nucleosides have anti-HIV activity in vitro and the inosine analogue is being clinically evaluated. The instability of these compounds toward acidic conditions complicates oral administration. The effect of the addition of a fluorine atom to the 2'-position was investigated by preparing the fluorine-containing 2'-erythro and 2'-threo isomers of ddA and the threo isomer of ddI. All fluorine-containing compounds were indefinitely stable to acidic conditions which completely decomposed ddI (1) and ddA (2) in minutes. While the fluorine-containing erythro isomer, 5, was inactive, the threo isomers, 2'-F-dd-ara-A (3) and 2'-F-dd-ara-I (4), were just as potent and active in protecting CD4+ ATH8 cells from the cytopathogenic effects of HIV-1 as the parent drugs. Exposure to pH 1 at 37 degrees C prior to testing destroyed the activity of ddA and ddI but left the anti-HIV properties of 3 and 4 unchanged. The fluorinated analogues also protected cells exposed to HIV-2 and inhibited gag gene product expression but not as effectively as the parent compounds. The fluorine-containing analogues appear to be somewhat more toxic in vitro to the antigen- and mitogen-driven proliferation of immunocompetent cells than their corresponding parent compounds.

  DOI：

  10.1021/jm00165a015

文献信息

• The β-Fluorine Effect. Electronic Versus Steric Effects in Radical Deoxygenations of Fluorine-Containing Pentofuranose Nucleosides
  作者：Stanislaw F. Wnuk、Dania R. Companioni、Vladimir Neschadimenko、Morris J. Robins

  DOI：10.1021/jo020428b

  日期：2002.12.1

  Stereoselective pyramidalization of free radicals by a vicinal fluorine substituent, the beta-fluorine effect, was invoked to rationalize a 77:23 anti/syn ratio of 2-deuterio-1-fluorocyclopentanes obtained by radical reduction of trans-2-fluoro-1-bromocyclopentane with tributyltin deuteride (Dolbier, W. R., Jr.; Bartberger, M. D. J. Org. Chem. 1995, 60, 4984-4985). We have evaluated analogous reductions

  借助邻位氟取代基对自由基进行立体选择性锥体化，即β-氟效应，以合理化通过反式-2-氟-1-基的自由基还原而获得的2-氘-1-氟环戊烷的77:23反/同比例。溴环戊烷和氘化三丁基锡（Dolbier，WR，Jr .; Bartberger，MDJ Org.Chem。1995，60，4984-4985）。我们已经评估了某些腺嘌呤2'（3'）-氟-3'（2'）-O-苯氧基硫羰基核苷衍生物的四种可能的立体异构体的类似还原。在所有情况下，腺嘌呤在β面上的立体作用都将氘从锡烷转移到呋喃糖环的α面上的C2'（C3'）。然而，β-氟效应增加了氘转移与邻位氟取代基的比率。
• Acid-stable 2'-fluoro purine dideoxynucleosides as active agents against HIV
  作者：Victor E. Marquez、Christopher K. H. Tseng、Hiroaki Mitsuya、Shizuko Aoki、James A. Kelley、Harry Ford、Jeri S. Roth、Samuel Broder、David G. Johns、John S. Driscoll

  DOI：10.1021/jm00165a015

  日期：1990.3

  2',3'-Dideoxy purine nucleosides have anti-HIV activity in vitro and the inosine analogue is being clinically evaluated. The instability of these compounds toward acidic conditions complicates oral administration. The effect of the addition of a fluorine atom to the 2'-position was investigated by preparing the fluorine-containing 2'-erythro and 2'-threo isomers of ddA and the threo isomer of ddI. All fluorine-containing compounds were indefinitely stable to acidic conditions which completely decomposed ddI (1) and ddA (2) in minutes. While the fluorine-containing erythro isomer, 5, was inactive, the threo isomers, 2'-F-dd-ara-A (3) and 2'-F-dd-ara-I (4), were just as potent and active in protecting CD4+ ATH8 cells from the cytopathogenic effects of HIV-1 as the parent drugs. Exposure to pH 1 at 37 degrees C prior to testing destroyed the activity of ddA and ddI but left the anti-HIV properties of 3 and 4 unchanged. The fluorinated analogues also protected cells exposed to HIV-2 and inhibited gag gene product expression but not as effectively as the parent compounds. The fluorine-containing analogues appear to be somewhat more toxic in vitro to the antigen- and mitogen-driven proliferation of immunocompetent cells than their corresponding parent compounds.