thymidine 5'-[3-hydroxymethoxy-2,2-bis(ethoxycarbonyl)]propylphosphate | 1161393-38-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: thymidine 5'-[3-hydroxymethoxy-2,2-bis(ethoxycarbonyl)]propylphosphate
• 英文别名: diethyl 2-[[hydroxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphoryl]oxymethyl]-2-(hydroxymethoxymethyl)propanedioate
• CAS: 1161393-38-9
• 化学式: C₂₀H₃₁N₂O₁₄P
• 分子量: 554.445
• InChiKey: NRMWUEJLHKKUET-RRFJBIMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  37
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  217
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  thymidine 5'-[3-hydroxymethoxy-2,2-bis(ethoxycarbonyl)]propylphosphate 在 sodium hydroxide 、 水 、 sodium chloride 、 4-羟乙基哌嗪乙磺酸 作用下， 生成 thymidine 5'-[3-hydroxy-2,2-bis(ethoxycarbonyl)propyl]phosphate
  参考文献：
  名称：

  Biodegradable Protections for Nucleoside 5′-Monophosphates: Comparative Study on the Removal of O-Acetyl and O-Acetyloxymethyl Protected 3-Hydroxy-2,2-bis(ethoxycarbonyl)propyl Groups

  摘要：

  The applicability of 3-acetyloxy-2,2-bis(ethoxycarbonyl)propyl and 3-acetyloxymethoxy-2,2-bis(ethoxycarbonyl)propyl groups as biodegradable phosphate protecting groups for nucleoside 5'-monophosphates has been studied in a HEPES buffer at pH 7.5. Enzymatic deacetylation with porcine carboxyesterase triggers the removal of the resulting 3 -hydroxy-2,2-bis(ethoxycarbonyl)propyl and 3-hydroxymethoxy-2,2-bis(ethoxycarbonyl)propyl groups by retro-aldol condensation and consecutive half acetal hydrolysis and retro-aldol condensation, respectively. The kinetics of these multistep deprotection reactions have been followed by HPLC, using appropriately protected thymidine 5'-monophosphates as model compounds. The enzymatic deacetylation of the 3-acetyloxymethoxy-2,2-bis(ethoxycarbonyl)propyl 5'-triester (2) is 25-fold faster than the deacetylation of its 3-acetyloxy-2,2-bis(ethoxycarbonyl)propyl-protected counterpart 1, and the difference in the deacetylation rates of the resulting diesters, 12b and 12a, is even greater. With 2, conversion to thymidine 5'-monophosphate (5'-TMP) is quantitative, while conversion of 1 to 5'-TMP is accompanied by formation of thymidine. Consistent with the preceding observations, quantitative release of 5'-TMP from 2 has been shown to take place in a whole cell extract of human prostate cancer cells.

  DOI：

  10.1021/jo9005987
• 作为产物：
  描述：

  thymidine 5'-[3-acetyloxymethoxy-2,2-bis(ethoxycarbonyl)]propylphosphate 在 sodium hydroxide 、 水 、 sodium chloride 、 porcine liver carboxyesterase 、 4-羟乙基哌嗪乙磺酸 作用下， 生成 thymidine 5'-[3-hydroxymethoxy-2,2-bis(ethoxycarbonyl)]propylphosphate
  参考文献：
  名称：

  Biodegradable Protections for Nucleoside 5′-Monophosphates: Comparative Study on the Removal of O-Acetyl and O-Acetyloxymethyl Protected 3-Hydroxy-2,2-bis(ethoxycarbonyl)propyl Groups

  摘要：

  The applicability of 3-acetyloxy-2,2-bis(ethoxycarbonyl)propyl and 3-acetyloxymethoxy-2,2-bis(ethoxycarbonyl)propyl groups as biodegradable phosphate protecting groups for nucleoside 5'-monophosphates has been studied in a HEPES buffer at pH 7.5. Enzymatic deacetylation with porcine carboxyesterase triggers the removal of the resulting 3 -hydroxy-2,2-bis(ethoxycarbonyl)propyl and 3-hydroxymethoxy-2,2-bis(ethoxycarbonyl)propyl groups by retro-aldol condensation and consecutive half acetal hydrolysis and retro-aldol condensation, respectively. The kinetics of these multistep deprotection reactions have been followed by HPLC, using appropriately protected thymidine 5'-monophosphates as model compounds. The enzymatic deacetylation of the 3-acetyloxymethoxy-2,2-bis(ethoxycarbonyl)propyl 5'-triester (2) is 25-fold faster than the deacetylation of its 3-acetyloxy-2,2-bis(ethoxycarbonyl)propyl-protected counterpart 1, and the difference in the deacetylation rates of the resulting diesters, 12b and 12a, is even greater. With 2, conversion to thymidine 5'-monophosphate (5'-TMP) is quantitative, while conversion of 1 to 5'-TMP is accompanied by formation of thymidine. Consistent with the preceding observations, quantitative release of 5'-TMP from 2 has been shown to take place in a whole cell extract of human prostate cancer cells.

  DOI：

  10.1021/jo9005987

文献信息

• Biodegradable Protections for Nucleoside 5′-Monophosphates: Comparative Study on the Removal of <i>O</i>-Acetyl and <i>O</i>-Acetyloxymethyl Protected 3-Hydroxy-2,2-bis(ethoxycarbonyl)propyl Groups
  作者：Mikko Ora、Sharmin Taherpour、Risto Linna、Anna Leisvuori、Emilia Hietamäki、Päivi Poijärvi-Virta、Leonid Beigelman、Harri Lönnberg

  DOI：10.1021/jo9005987

  日期：2009.7.17

  The applicability of 3-acetyloxy-2,2-bis(ethoxycarbonyl)propyl and 3-acetyloxymethoxy-2,2-bis(ethoxycarbonyl)propyl groups as biodegradable phosphate protecting groups for nucleoside 5'-monophosphates has been studied in a HEPES buffer at pH 7.5. Enzymatic deacetylation with porcine carboxyesterase triggers the removal of the resulting 3 -hydroxy-2,2-bis(ethoxycarbonyl)propyl and 3-hydroxymethoxy-2,2-bis(ethoxycarbonyl)propyl groups by retro-aldol condensation and consecutive half acetal hydrolysis and retro-aldol condensation, respectively. The kinetics of these multistep deprotection reactions have been followed by HPLC, using appropriately protected thymidine 5'-monophosphates as model compounds. The enzymatic deacetylation of the 3-acetyloxymethoxy-2,2-bis(ethoxycarbonyl)propyl 5'-triester (2) is 25-fold faster than the deacetylation of its 3-acetyloxy-2,2-bis(ethoxycarbonyl)propyl-protected counterpart 1, and the difference in the deacetylation rates of the resulting diesters, 12b and 12a, is even greater. With 2, conversion to thymidine 5'-monophosphate (5'-TMP) is quantitative, while conversion of 1 to 5'-TMP is accompanied by formation of thymidine. Consistent with the preceding observations, quantitative release of 5'-TMP from 2 has been shown to take place in a whole cell extract of human prostate cancer cells.