diphenyl 4-hydroxybutyl phosphate | 132649-26-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: diphenyl 4-hydroxybutyl phosphate
• 英文别名: 4-Hydroxybutyl diphenyl phosphate
• CAS: 132649-26-4
• 化学式: C₁₆H₁₉O₅P
• 分子量: 322.298
• InChiKey: AJXKKVKPCKGZNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diphenyl 4-hydroxybutyl phosphate 在 吡啶 、 2-氯-1,3,2-苯并二氧磷杂环己烷-4-酮 、 三乙胺 作用下， 以 1,4-二氧六环 、 吡啶 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 4-Bis(trimethylsilyloxy)phosphanyloxybutyl diphenyl phosphate
  参考文献：
  名称：

  Solid-Phase Synthesis of Thermolytic DNA Oligonucleotides Functionalized with a Single 4-Hydroxy-1-butyl or 4-Phosphato-/Thiophosphato-1-butyl Thiophosphate Protecting Group

  摘要：

  Several thermolytic CpG-containing DNA oligonucleotides analogous to 1 have been synthesized to serve as potential immunotherapeutic oligonucleotide prodrug formulations for the treatment of infectious diseases in animal models. Specifically, the CpG motif (GACGTT) of each DNA oligonucleotide has been functionalized with either the thermolabile 4-hydroxy-1-butyl or the 4-phosphato-/thiophosphato-1-butyl thiophosphate protecting group. This functionalization was achieved through incorporation of activated deoxyribonucleoside phosphoramidite 8b into the oligonucleotide chain during solid-phase synthesis and, optionally, through subsequent phosphorylation effected by phosphoramidite 9. Complete conversion of CpG ODNs hbu1555, psb1555, and pob1555 to CpG ODN 1555 (homologous to 2) occurred under elevated temperature conditions, thereby validating the function of these diastereomeric oligonucleotides as prodrugs in vitro. Noteworthy is the significant increase in solubility of CpG ODN psb1555 and CpG pob1555 in water when compared to that of neutral CpG ODN fma1555 (homologous to 1).

  DOI：

  10.1021/jo062087y
• 作为产物：
  描述：

  1,4-丁二醇 、 氯磷酸二苯酯 在 N,N-二异丙基乙胺 作用下， 以 苯 为溶剂， 反应 1.0h， 以77%的产率得到diphenyl 4-hydroxybutyl phosphate
  参考文献：
  名称：

  Solid-Phase Synthesis of Thermolytic DNA Oligonucleotides Functionalized with a Single 4-Hydroxy-1-butyl or 4-Phosphato-/Thiophosphato-1-butyl Thiophosphate Protecting Group

  摘要：

  Several thermolytic CpG-containing DNA oligonucleotides analogous to 1 have been synthesized to serve as potential immunotherapeutic oligonucleotide prodrug formulations for the treatment of infectious diseases in animal models. Specifically, the CpG motif (GACGTT) of each DNA oligonucleotide has been functionalized with either the thermolabile 4-hydroxy-1-butyl or the 4-phosphato-/thiophosphato-1-butyl thiophosphate protecting group. This functionalization was achieved through incorporation of activated deoxyribonucleoside phosphoramidite 8b into the oligonucleotide chain during solid-phase synthesis and, optionally, through subsequent phosphorylation effected by phosphoramidite 9. Complete conversion of CpG ODNs hbu1555, psb1555, and pob1555 to CpG ODN 1555 (homologous to 2) occurred under elevated temperature conditions, thereby validating the function of these diastereomeric oligonucleotides as prodrugs in vitro. Noteworthy is the significant increase in solubility of CpG ODN psb1555 and CpG pob1555 in water when compared to that of neutral CpG ODN fma1555 (homologous to 1).

  DOI：

  10.1021/jo062087y

文献信息

• Cyclophosphamide potentiation and aldehyde oxidase inhibition by phosphorylated aldehydes and acetals
  作者：Lindley A. Cates、Gerald S. Jones、Daniel J. Good、Helen Y. L. Tsai、Ven-Shun Li、Norman Caron、Shiao-Chun Tu、Aubrey P. Kimball

  DOI：10.1021/jm00177a018

  日期：1980.3

  Fourteen phosphorylated acetals and aldehydes were synthesized for testing in vitro as inhibitors or substrates of aldehyde oxidase, an enzyme involved in the conversion of aldophosphamide to inactive carboxyphosphamide, and for concurrent in vivo administration with cyclophosphamide to mice bearing L1210 ascites tumor cells. Five phosphorus derivatives gave Ki values of 0.1--0.3 mM compared to 0.03 mM for pyridoxal, as determined in aldehyde oxidase assays using N-methylnicotinamide as the substrate. The most active phosphorus inhibitor, ethyl phenyl(2-formylethyl)phosphinate (2b), and pyridoxal were further shown to give competitive and mixed inhibition, respectively. Three aldehydes, administered concurrently with cyclophosphamide, produced greater increases in life span of L1210-implanted mice than did pyridoxal. All four agents gave an average increase in life span greater than 50% over that shown by cyclophosphamide alone.
• Solid-Phase Synthesis of Thermolytic DNA Oligonucleotides Functionalized with a Single 4-Hydroxy-1-butyl or 4-Phosphato-/Thiophosphato-1-butyl Thiophosphate Protecting Group
  作者：Andrzej Grajkowski、Cristina Ausín、Jon S. Kauffman、John Snyder、Sonja Hess、John R. Lloyd、Serge L. Beaucage

  DOI：10.1021/jo062087y

  日期：2007.2.1

  Several thermolytic CpG-containing DNA oligonucleotides analogous to 1 have been synthesized to serve as potential immunotherapeutic oligonucleotide prodrug formulations for the treatment of infectious diseases in animal models. Specifically, the CpG motif (GACGTT) of each DNA oligonucleotide has been functionalized with either the thermolabile 4-hydroxy-1-butyl or the 4-phosphato-/thiophosphato-1-butyl thiophosphate protecting group. This functionalization was achieved through incorporation of activated deoxyribonucleoside phosphoramidite 8b into the oligonucleotide chain during solid-phase synthesis and, optionally, through subsequent phosphorylation effected by phosphoramidite 9. Complete conversion of CpG ODNs hbu1555, psb1555, and pob1555 to CpG ODN 1555 (homologous to 2) occurred under elevated temperature conditions, thereby validating the function of these diastereomeric oligonucleotides as prodrugs in vitro. Noteworthy is the significant increase in solubility of CpG ODN psb1555 and CpG pob1555 in water when compared to that of neutral CpG ODN fma1555 (homologous to 1).