diisopropyl (S)-{[(1-fluoro-3-hydroxypropan-2-yl)oxy]-methyl}phosphonate | 151223-10-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: diisopropyl (S)-{[(1-fluoro-3-hydroxypropan-2-yl)oxy]-methyl}phosphonate
• 英文别名: diisopropyl (S)-{[(1-fluoro-3-hydroxypropan-2-yl)oxy]methyl}phosphonate；(S)-2-diisopropylphosphonylmethoxy-3-fluoropropanol
• CAS: 151223-10-8
• 化学式: C₁₀H₂₂FO₅P
• 分子量: 272.254
• InChiKey: QCMKVSZMJUFTLP-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.33
• 重原子数：
  17.0
• 可旋转键数：
  9.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  64.99
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  diisopropyl (S)-{[(1-fluoro-3-hydroxypropan-2-yl)oxy]-methyl}phosphonate 在 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 2.75h， 生成
  参考文献：
  名称：

  Synthesis and antiviral activity of N9-[3-fluoro-2-(phosphonomethoxy)propyl] analogues derived from N6-substituted adenines and 2,6-diaminopurines

  摘要：

  An efficient method for the synthesis of N-9-[3-fluoro-2-(phosphonomethoxy) propyl] (FPMP) derivatives of purine bases has been developed. Both (R)- and (S)-enantiomers of the N-6-substituted FPMP derivatives of adenine and 2,6-diaminopurine were prepared and their anti-human immunodeficiency virus (HIV) and anti-Moloney murine sarcoma virus (MSV) activity was evaluated. Whereas none of the 6-substituted FPMPA derivatives showed any antiviral activity, several FPMPDAP derivatives had a moderate antiretroviral activity. Moreover, the data obtained from the study of the substrate activity of the active derivatives towards N-6-methyl-AMP aminohydrolase support the notion that the studied N-6-substituted FPMPDAP derivatives act as prodrugs of the antiretroviral FPMPG analogues. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.050
• 作为产物：
  描述：

  (S)-3-O-benzyl-2-O-<(diisopropylphosphono)methyl>-1-O-(methylsulfonyl)glycerol 在 三氯化硼 、 tri-n-butylamine hydrofluoride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 diisopropyl (S)-{[(1-fluoro-3-hydroxypropan-2-yl)oxy]-methyl}phosphonate
  参考文献：
  名称：

  2'-取代的9- [2-（膦酰基甲氧基）乙基]鸟嘌呤类似物的合成和抗病毒活性。

  摘要：

  已经合成了一系列9- [2-（膦酰基甲氧基）乙基]鸟嘌呤（PMEG，1）的2'-取代衍生物，并在XTT分析中体外评估了其抗人免疫缺陷病毒（HIV）的活性以及对斑减少试验中的疱疹活性。已经观察到这些衍生物的抗HIV活性取决于取代基的大小和性质以及在PMEG 2'-位的手性。此外，与疱疹病毒相比，这些化合物通常具有更大的抗HIV活性。这些研究中出现的最有趣的类似物是（R）-2'-（叠氮基甲基）-PMEG [[R] -5]和（R）-2'-乙烯基-PMEG [[R-11]]。前者在CEM细胞中显示出抗HIV活性，IC50为5 microM，细胞毒性（CC50）大于1.4 mM。后者的抗HIV活性IC50为13 microM，CC50大于1.6 mM。此外，我们已经证明用胞嘧啶取代这些2'-取代的PMEG类似物的鸟嘌呤碱基会大大降低抗HIV和抗疱疹的活性。

  DOI：

  10.1021/jm00071a003

文献信息

• Synthesis of fluorinated acyclic nucleoside phosphonates with 5-azacytosine base moiety
  作者：Karel Pomeisl、Marcela Krečmerová、Radek Pohl、Robert Snoeck、Graciela Andrei

  DOI：10.1016/j.tet.2019.130529

  日期：2019.9

  With respect to the strong antiviral activity of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine various types of its side chain fluorinated analogues were prepared. The title compound, (S)-1-[3-fluoro-2-(phosphonomethoxy)propyl]-5-azacytosine (FPMP-5-azaC) was synthesised by the condensation reaction of (S)-2-[(diisopropoxyphosphoryl)methoxy)-3-fluoropropyl p-toluenesulfonate with a sodium

  关于（S）-1- [3-羟基-2-（膦酰基甲氧基）丙基] -5-氮杂胞嘧啶的强抗病毒活性，制备了各种类型的其侧链氟化类似物。通过（S）-2-[（二异丙氧基磷酰基）的缩合反应，合成标题化合物（S）-1- [3-氟-2-（膦甲氧基）丙基] -5-氮杂胞嘧啶（FPMP-5-azaC ）。甲磺酸）-3-氟丙基对甲苯磺酸盐与5-氮杂胞嘧啶钠盐的混合物，然后分离出合适的N 1和O 2区域异构体和酯水解。FPMP-5-azaC对其5,6-dihydro-5-azacytosine对应物，氨基酸氨基磷酸酯前药和具有退火五元咪唑环的系统的转化，即咪唑[1,2-a] [1,3,5还进行了三嗪衍生物。由5-氮杂胞嘧啶和三氟甲基环氧乙烷制备1-（2-膦甲氧基-3,3,3-三氟丙基）-5-氮杂胞嘧啶以形成1-（3,3,3-三氟-2-羟丙基）-5-氮杂胞嘧啶用二异丙基溴甲烷膦酸酯处理，然后将酯脱保护。研究了所有新制备
• Synthesis of N-(3-Fluoro-2-phosphonomethoxypropyl) (FPMP) Derivatives of Heterocyclic Bases
  作者：Jindřich Jindřich、Antonín Holý、Hana Dvořáková

  DOI：10.1135/cccc19931645

  日期：——

  A new group of compounds has been prepared: N-(3-fluoro-2-phosphonomethoxypropyl) (FPMP) derivatives of purine and pyrimidine bases which exhibit a significant selective activity against a broad spectrum of retroviruses. Racemic N-(3-fluoro-2-phosphonomethoxypropyl) derivatives of adenin (V), guanine (IX), cytosine (XIII), 2,6-diaminopurine (XXI), 3-deazaadenin e(XVII), xanthine (X) and hypoxanthin (VI) were prepared from the corresponding N-(3-fluoro-2-hydroxypropyl) derivatives after protection of amino group at the heterocyclic ring by selective benzoylation, reaction with diisopropyl p-toluenesulfonyloxymethylphosphonate (II), and subsequent removal of the protecting groups. Chiral FPMP derivatives were prepared by reaction of heterocyclic base with the corresponding chiral synthon (XXX, XXXVII) followed by deprotection. The required chiral synthons were obtained from enantiomeric 3-fluoro-1,2-propanediols by two methods. In the first, the primary hydroxyl group was tritylated, the obtained derivative was reacted with compound II, the trityl group was removed and the product was mesylated to give synthon XXXVII. The second pathway consisted in selective tosylation of the primary hydroxyl group and conversion of the secondary hydroxyl into the acetoxymethyl ether via the methoxymethyl ether; treatment of the acetoxy compound with bromotrimethylsilane and triisopropyl phosphite afforded the desired synthon XXX.

  已合成一组新化合物：嘌呤和嘧啶碱基的N-(3-氟-2-磷甲氧基丙基)（FPMP）衍生物，对广谱逆转录病毒表现出显著的选择性活性。从相应的N-(3-氟-2-羟基丙基)衍生物经过异构环上氨基选择性苯甲酰化、与异丙基对甲苯磺酰氧甲基磷酸二异丙酯（II）反应，以及随后去除保护基制备了腺嘌呤（V）、鸟嘌呤（IX）、胞嘧啶（XIII）、2,6-二氨基嘌呤（XXI）、3-去氧腺嘌呤（XVII）、黄嘌呤（X）和次黄嘌呤（VI）的消旋N-(3-氟-2-磷甲氧基丙基)衍生物。手性FPMP衍生物通过异构碱基与相应的手性合成物（XXX、XXXVII）反应后去保护基制备。所需的手性合成物是通过两种方法从对映异构体3-氟-1,2-丙二醇获得的。在第一种方法中，首要羟基进行三苯甲酰化，得到的衍生物与化合物II反应，去除三苯甲基基团，然后进行甲磺酰化以得到合成物XXXVII。第二种途径包括选择性对磺酰化首要羟基，将次要羟基转化为乙酰氧甲基醚通过甲氧基甲基醚；将乙酰氧化合物与溴三甲基硅烷和三异丙基磷酸酯处理后得到所需的合成物XXX。