[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxymethyl]-phosphonic acid diethyl ester | 142613-36-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: [2-(tert-Butyl-dimethyl-silanyloxy)-ethoxymethyl]-phosphonic acid diethyl ester
• 英文别名: Tert-butyl-[2-(diethoxyphosphorylmethoxy)ethoxy]-dimethylsilane
• CAS: 142613-36-3
• 化学式: C₁₃H₃₁O₅PSi
• 分子量: 326.445
• InChiKey: CUNOTZYLIVRDNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.25
• 重原子数：
  20
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [2-(tert-Butyl-dimethyl-silanyloxy)-ethoxymethyl]-phosphonic acid diethyl ester 在 Dowex 50WX8 、 仲丁基锂 、 caesium carbonate 、 N-氟代双苯磺酰胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.5h， 生成 4-Amino-1-[2-[diethoxyphosphoryl(fluoro)methoxy]ethyl]pyrimidin-2-one
  参考文献：
  名称：

  Synthesis and antiviral activities of fluorinated acyclic nucleoside phosphonates

  摘要：

  合成了新的α-氟衍生物PME和HPMP，具体通过电亲核氟化反应将1-叔丁基二甲基硅氧基-2-[(二乙氧基磷酸基)甲氧基]乙烷15和3-O-苄基-2-O-[(二乙氧基磷酸基)甲基]-1-O-(叔丁基二甲基硅氧基)甘油22进行合成。第一系列具有α-氟（磷酸基）甲氧基基团的非环状核苷酸磷酸酯是通过F-PME或F-HPMP衍生物18、26或27与相应的嘌呤或嘧啶核酸碱基在修改的Mitsunobu条件或碱催化烷基化条件下偶联制备的。对F-PMEA 25a-c、F-PMEG 25f和F-PMEC 25g的二酯与浓氨水处理后，形成了相应的单乙基磷酸盐30a、30d、30f和30g的单铵盐。合成的氟化非环状核苷酸磷酸酯经过了对抗单纯疱疹病毒、呼吸道病毒、乙型肝炎病毒和HIV的测试。F-PMEA的单乙基酯单铵盐30a显示出对人细胞巨病毒（HCMV）、埃博拉病毒和麻疹的活性，其EC50值分别为5.6、1.6和32 µg mL–1。

  DOI：

  10.1039/a805929b
• 作为产物：
  描述：

  2-((二乙氧基膦酰爪基)甲氧基)乙基醋酸盐 在 4-二甲氨基吡啶 、 sodium hydride 、 N-氟代双苯磺酰胺 、 三乙胺 作用下， 生成 [2-(tert-Butyl-dimethyl-silanyloxy)-ethoxymethyl]-phosphonic acid diethyl ester
  参考文献：
  名称：

  Introduction of α-fluorophosphonomethyl ether functionality and its application to the synthesis of fluorinated acyclic phosphonate nucleosides

  摘要：

  Introduction of the alpha-fluorophosphonomethyl ether functionality has been achieved by electrophilic fluorination of the corresponding phosphonomethyl ether carbanion. Coupling of the synthesized 2-[(diethoxyphosphono)fluoromethoxy]ethanol (9) with adenine and 6-chloropurine under Mitsunobu conditions afforded novel fluorinated acyclic phosphonate nucleosides 11a and 11b, respectively. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0040-4039(96)02106-5

文献信息

• Synthesis and antiviral activity of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine
  作者：Kuo Long Yu、Joanne J. Bronson、Hyekyung Yang、Amy Patick、Masud Alam、Vera Brankovan、Roelf Datema、Michael J. M. Hitchcock、John C. Martin

  DOI：10.1021/jm00094a005

  日期：1992.8

  A number of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG, 1) have been synthesized and tested in vitro for anti-herpes and anti-human immunodeficiency virus (HIV) activity. Among these analogues, (R)-2'-methyl-PMEG [(R)-3] and 2',2'-dimethyl-PMEG (7) demonstrated potent anti-HIV activity in the XTT assay with EC50 values of 1.0 and 2.6 microM, respectively. The corresponding (S)-2'-methyl-PMEG

  已经合成了许多9- [2-（膦甲氧基）乙基]鸟嘌呤的甲基衍生物（PMEG，1），并在体外测试了其抗疱疹和抗人免疫缺陷病毒（HIV）的活性。在这些类似物中，（R）-2'-甲基-PMEG [[R] -3]和2'，2'-二甲基-PMEG（7）在XTT分析中显示出有效的抗HIV活性，EC50值为1.0和分别为2.6 microM。发现相应的（S）-2'-甲基-PMEG [（S）-3]对HIV的效力较低。另外，制备9- [3-羟基-2-（膦甲氧基）丙基]鸟嘌呤的（R）和（S）对映异构体（HPMPG，8）用于比较生物学活性，并显示出对疱疹病毒的活性和等效性。 ，但对HIV无效。
• Synthesis and antiviral activities of fluorinated acyclic nucleoside phosphonates
  作者：Wei Chen、Michael T. Flavin、Robert Filler、Ze-Qi Xu

  DOI：10.1039/a805929b

  日期：——

  Novel α-fluoro derivatives of PME and HPMP were synthesized by electrophilic fluorination of 1-tert-butyldimethylsiloxy-2-[(diethoxyphosphoryl)methoxy]ethane 15 and 3-O-benzyl-2-O-[(diethoxyphosphoryl)methyl]-1-O-(tert-butyldimethylsiloxy)glycerol 22, respectively. The first series of acyclic nucleoside phosphonates possessing the α-fluoro(phosphoryl)methoxy group were prepared by coupling of F-PME or F-HPMP derivatives 18, 26, or 27 with the corresponding purine or pyrimidine nucleic bases under either modified Mitsunobu conditions or base-catalyzed alkylation conditions. Treatment of the diesters of F-PMEA 25a–c, F-PMEG 25f and F-PMEC 25g with concentrated aqueous ammonia led to the formation of the corresponding monoammonium salts of monoethyl phosphonate 30a, 30d, 30f and 30g. The synthesized fluorinated acyclic nucleoside phosphonates were tested against herpes viruses, respiratory viruses, hepatitis B virus and HIV. The monoammonium salt of the monoethyl ester of F-PMEA 30a was found to be active against human cytomegalovirus (HCMV), Epstein–Barr virus and measles with EC50 values of 5.6, 1.6 and 32 µg mL–1, respectively.

  合成了新的α-氟衍生物PME和HPMP，具体通过电亲核氟化反应将1-叔丁基二甲基硅氧基-2-[(二乙氧基磷酸基)甲氧基]乙烷15和3-O-苄基-2-O-[(二乙氧基磷酸基)甲基]-1-O-(叔丁基二甲基硅氧基)甘油22进行合成。第一系列具有α-氟（磷酸基）甲氧基基团的非环状核苷酸磷酸酯是通过F-PME或F-HPMP衍生物18、26或27与相应的嘌呤或嘧啶核酸碱基在修改的Mitsunobu条件或碱催化烷基化条件下偶联制备的。对F-PMEA 25a-c、F-PMEG 25f和F-PMEC 25g的二酯与浓氨水处理后，形成了相应的单乙基磷酸盐30a、30d、30f和30g的单铵盐。合成的氟化非环状核苷酸磷酸酯经过了对抗单纯疱疹病毒、呼吸道病毒、乙型肝炎病毒和HIV的测试。F-PMEA的单乙基酯单铵盐30a显示出对人细胞巨病毒（HCMV）、埃博拉病毒和麻疹的活性，其EC50值分别为5.6、1.6和32 µg mL–1。
• Introduction of α-fluorophosphonomethyl ether functionality and its application to the synthesis of fluorinated acyclic phosphonate nucleosides
  作者：Wei Chen、Michael T. Flavin、Robert Filler、Ze-Qi Xu

  DOI：10.1016/s0040-4039(96)02106-5

  日期：1996.12

  Introduction of the alpha-fluorophosphonomethyl ether functionality has been achieved by electrophilic fluorination of the corresponding phosphonomethyl ether carbanion. Coupling of the synthesized 2-[(diethoxyphosphono)fluoromethoxy]ethanol (9) with adenine and 6-chloropurine under Mitsunobu conditions afforded novel fluorinated acyclic phosphonate nucleosides 11a and 11b, respectively. Copyright (C) 1996 Elsevier Science Ltd