diethyl <4-hydroxy-3-(hydroxymethyl)butyl>phosphonate | 133866-77-0

• 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: diethyl <4-hydroxy-3-(hydroxymethyl)butyl>phosphonate
• 英文别名: 2-(2'-diethylphosphono)ethyl-1,3-propanediol；Diethyl 4-hydroxy-3-(hydroxymethyl)butyl-phosphonate；2-(2-diethoxyphosphorylethyl)propane-1,3-diol
• CAS: 133866-77-0
• 化学式: C₉H₂₁O₅P
• 分子量: 240.237
• InChiKey: DXWHFZRAZQRMPC-UHFFFAOYSA-N

物化性质

• 沸点：
  388.9±32.0 °C(Predicted)
• 密度：
  1.147±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  15
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl <4-hydroxy-3-(hydroxymethyl)butyl>phosphonate 在 吡啶 、 4-二甲氨基吡啶 、 TEA 、 caesium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 9-[4-diethoxyphosphoryl-2-[[(4-methoxyphenyl)-diphenylmethoxy]methyl]butyl]purin-6-amine
  参考文献：
  名称：

  A new class of acyclic phosphonate nucleotide analogs: Phosphonate isosteres of acyclovir and ganciclovir monophosphates as antiviral agents

  摘要：

  Novel phosphonate isosteres of acyclovir (ACV) and ganciclovir (DHPG) monophosphates (20 and 32) were found to be potent and selective antiherpesvirus agents. In the series of phosphonate analogues of ACV monophosphate, only the guanine analogue 20 exhibited activity against herpesviruses, similar to the structure-activity relationship observed for base modification of ACV analogues. The phosphonate isostere of ACV monophosphate (20) was more effective than ACV in the HSV-1 infected mouse model. The 3'-carba analogues of 9-[3-hydroxy-2-(phosphonomethoxy)propyl]purines/pyrimidines (adenine, HPMPA; guanine, HPMPG; cytosine, HPMPC) are devoid of antiherpesvirus activity. This result confirms that the beta-oxygen atom of the phosphonomethyl ether functionality in HPMP-purines/pyrimidines plays a critical role for activity against herpesviruses.

  DOI：

  10.1021/jm00111a052
• 作为产物：
  描述：

  5-(2-iodoethyl)-2,2-dimethyl-1,3-dioxane 在 盐酸 作用下， 以 丙酮 为溶剂， 反应 1.67h， 生成 diethyl <4-hydroxy-3-(hydroxymethyl)butyl>phosphonate
  参考文献：
  名称：

  A new class of acyclic phosphonate nucleotide analogs: Phosphonate isosteres of acyclovir and ganciclovir monophosphates as antiviral agents

  摘要：

  Novel phosphonate isosteres of acyclovir (ACV) and ganciclovir (DHPG) monophosphates (20 and 32) were found to be potent and selective antiherpesvirus agents. In the series of phosphonate analogues of ACV monophosphate, only the guanine analogue 20 exhibited activity against herpesviruses, similar to the structure-activity relationship observed for base modification of ACV analogues. The phosphonate isostere of ACV monophosphate (20) was more effective than ACV in the HSV-1 infected mouse model. The 3'-carba analogues of 9-[3-hydroxy-2-(phosphonomethoxy)propyl]purines/pyrimidines (adenine, HPMPA; guanine, HPMPG; cytosine, HPMPC) are devoid of antiherpesvirus activity. This result confirms that the beta-oxygen atom of the phosphonomethyl ether functionality in HPMP-purines/pyrimidines plays a critical role for activity against herpesviruses.

  DOI：

  10.1021/jm00111a052

文献信息

• Antiviral phosphonylalkoxy purines
  申请人：Beecham p.l.c.

  公开号：US05166198A1

  公开（公告）日：1992-11-24

  A compound of formula (I), or a pharmaceutically acceptable salt thereof: ##STR1## wherein R.sub.1 is hydroxy or amino; R.sub.2 is hydrogen or amino; R.sub.3 is hydrogen, hydroxymethyl or acyloxymethyl; R.sub.4 is hydrogen or (when R.sub.3 =H and Z is a bond or CH.sub.2) hydroxy, acyloxy, hydroxymethyl or acyloxymethyl; Z is a bond, or a group CHR.sub.8 wherein R.sub.8 is hydrogen, or (when R.sub.3 =R.sub.4 =H), R.sub.8 is hydroxy, acyloxy, hydroxymethyl or acyloxymethyl; R.sub.5 is a group of formula: ##STR2## wherein R.sub.6 and R.sub.7 are independently selected from hydrogen, C.sub.1-6 alkyl and optionally substituted phenyl.

  化合物的化学式（I），或其药学上可接受的盐：其中R₁为羟基或氨基；R₂为氢或氨基；R₃为氢、羟甲基或醋酰氧甲基；R₄为氢或（当R₃=H且Z为键或CH₂时）羟基、醋酰氧基、羟甲基或醋酰氧甲基；Z为键，或基团CHR₈，其中R₈为氢，或（当R₃=R₄=H时），R₈为羟基、醋酰氧基、羟甲基或醋酰氧甲基；R₅为下列基团：其中R₆和R₇分别选自氢、C₁-₆烷基和可选择取代的苯基。
• Phosphono derivatives of purine with antiviral activity
  申请人：Beecham Group p.l.c.

  公开号：EP0404296A1

  公开（公告）日：1990-12-27

  A compound of formula (I), or a pharmaceutically acceptable salt thereof: wherein R₁ is hydroxy or amino; R₂ is hydrogen or amino; R₃ is hydrogen, hydroxymethyl or acyloxymethyl; R₄ is hydrogen or (when R₃=H and Z is a bond or CH₂) hydroxy, acyloxy, hydroxymethyl or acyloxymethyl; Z is a bond, or a group CHR₈ wherein R₈ is hydrogen, or (when R₃=R₄=H), R₈ is hydroxy, acyloxy, hydroxymethyl or acyloxymethyl; R₅ is a group of formula: wherein R₆ and R₇ are independently selected from hydrogen, C₁₋₆ alkyl and optionally substituted phenyl.

  式 (I) 的化合物或其药学上可接受的盐： 其中 R₁ 是羟基或氨基； R₂ 是氢或氨基 R₃ 是氢、羟甲基或酰氧基甲基； R₄ 是氢或（当 R₃=H 且 Z 是键或 CH₂ 时）羟基、酰氧基、羟甲基或酰氧基甲基； Z 是键，或一个基团 CHR₈，其中 R₈ 是氢，或（当 R₃=R₄=H 时），R₈ 是羟基、酰氧基、羟甲基或酰氧基甲基； R₅ 是式中的基团： 其中 R₆ 和 R₇ 独立选自氢、C₁₋₆ 烷基和任选取代的苯基。
• Lipase-catalyzed enantioselective acylation of prochiral 2-(ω-phosphono)alkyl-1,3-propanediols: Application to the enantioselective synthesis of ω-phosphono-α-amino acids
  作者：Tsutomu Yokomatsu、Mutsumi Sato、Shiroshi Shibuya

  DOI：10.1016/0957-4166(96)00354-0

  日期：1996.9

  Lipase PS catalyzed acetylation of prochiral 2-(omega-phosphono)alkyl-1,3-propanediols 1a-c was found to proceed with high enantioselectivity. The applications of phosphonic chirons 2a-c thus obtained were illustrated by the stereocontrolled synthesis of omega-phosphono-alpha-amino acids such as L-AP-3, L-AP-4, and N-Boc-L-F(2)Pab(OEt)(2)-OH. Copyright (C) 1996 Published by Elsevier Science Ltd
• Synthesis and antiviral activity of new phosphonobutoxypurines
  作者：Michael R. Harnden、Halina T. Serafinowska

  DOI：10.1016/0960-894x(96)00400-3

  日期：1996.9

  A series of new 9-(4-phosphonobutoxy)purines was synthesized and evaluated as antiviral agents. 9-(4-Phosphonobutoxy)guanine displayed potent and selective activity against HIV-1 in peripheral blood lymphocytes. Copyright (C) 1996 Elsevier Science Ltd
• KIM, CHOUNG UN;MISCO, PETER F.;LUH, BING YU;HITCHCOCK, MICHAEL J. M.;GHAZ+, J. MED. CHEM., 34,(1991) N, C. 2286-2294
  作者：KIM, CHOUNG UN、MISCO, PETER F.、LUH, BING YU、HITCHCOCK, MICHAEL J. M.、GHAZ+

  DOI：——

  日期：——