(R)-1-hydroxy-2-(phosphonomethoxy)propane

• 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: (R)-1-hydroxy-2-(phosphonomethoxy)propane
• 英文别名: HPMP；[(2R)-1-hydroxypropan-2-yl]oxymethylphosphonic acid
• 化学式: C₄H₁₁O₅P
• 分子量: 170.102
• InChiKey: JTSVVSMIUFIGRT-SCSAIBSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-1-hydroxy-2-(phosphonomethoxy)propane 在 sodium hydroxide 、 sodium nitrate 、 barium(II) nitrate 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses

  摘要：

  The acyclic nucleoside phosphonate (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC; Cidofovir) has been approved for clinical use in antiviral therapy. We determined the acidity constants of H-2(HPMPC)(+/-), as well as that of the nucleobase-free (hydroxy-2-(phosphonomethoxy)propane (H(HPMP)(-)) (I = 0.1 M, NaNO3; 25 degrees C). Given that in vivo nucleotides and their analogues participate in reactions typically as metal ion (M2+) complexes, the stability constants of the M(H;HPMPC)(+), M(HPMPC), and M(HPMP) complexes with M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ were measured. Comparisons between results for HPMP2- and previous data for PME2- (CH3CH2-O-CH2PO32-; phosphonomethoxyethane) revealed the hydroxyl-group effect. The hydroxyl group stabilizes only complexes with the heavier alkaline earth metal ions (Ca2+, Sr2+, Ba2+). For all other complexes, the enhanced stability can solely be explained by the formation of 5-membered chelates involving the ether oxygen; these occur in equilibrium with simple 'open' phosphonate-M2+ species. The stability of the M(HPMPC) complexes is also higher than expected for a phosphonate-only coordination, indicating that chelates are formed, but comparison with the HPMP2- data shows that the cytosine base does not affect complex stability. Similar observations were made previously with related cytosine derivatives. The stability data for the monoprotonated M(H;HPMPC)(+) complexes suggest that these carry H+ predominantly on the phosphonate group, and M2+ on the nucleobase. (C) 2017 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ica.2017.06.011

文献信息

• Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses
  作者：Claudia A. Blindauer、Astrid Sigel、Bert P. Operschall、Antonín Holý、Helmut Sigel

  DOI：10.1016/j.ica.2017.06.011

  日期：2018.3

  The acyclic nucleoside phosphonate (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC; Cidofovir) has been approved for clinical use in antiviral therapy. We determined the acidity constants of H-2(HPMPC)(+/-), as well as that of the nucleobase-free (hydroxy-2-(phosphonomethoxy)propane (H(HPMP)(-)) (I = 0.1 M, NaNO3; 25 degrees C). Given that in vivo nucleotides and their analogues participate in reactions typically as metal ion (M2+) complexes, the stability constants of the M(H;HPMPC)(+), M(HPMPC), and M(HPMP) complexes with M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ were measured. Comparisons between results for HPMP2- and previous data for PME2- (CH3CH2-O-CH2PO32-; phosphonomethoxyethane) revealed the hydroxyl-group effect. The hydroxyl group stabilizes only complexes with the heavier alkaline earth metal ions (Ca2+, Sr2+, Ba2+). For all other complexes, the enhanced stability can solely be explained by the formation of 5-membered chelates involving the ether oxygen; these occur in equilibrium with simple 'open' phosphonate-M2+ species. The stability of the M(HPMPC) complexes is also higher than expected for a phosphonate-only coordination, indicating that chelates are formed, but comparison with the HPMP2- data shows that the cytosine base does not affect complex stability. Similar observations were made previously with related cytosine derivatives. The stability data for the monoprotonated M(H;HPMPC)(+) complexes suggest that these carry H+ predominantly on the phosphonate group, and M2+ on the nucleobase. (C) 2017 Elsevier B.V. All rights reserved.