(R)-3-O-Benzyl-2-O-<(diethylphosphonyl)methyl>-1-O-<(p-methoxyphenyl)diphenylmethyl>glycerol | 120362-28-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (R)-3-O-Benzyl-2-O-<(diethylphosphonyl)methyl>-1-O-<(p-methoxyphenyl)diphenylmethyl>glycerol
• 英文别名: 1-[[(2R)-2-(diethoxyphosphorylmethoxy)-3-phenylmethoxypropoxy]-diphenylmethyl]-4-methoxybenzene
• CAS: 120362-28-9
• 化学式: C₃₅H₄₁O₇P
• 分子量: 604.68
• InChiKey: NIRDOYWVOHDSOB-UUWRZZSWSA-N

物化性质

• 沸点：
  686.6±55.0 °C(Predicted)
• 密度：
  1.157±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.83
• 重原子数：
  43.0
• 可旋转键数：
  18.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  72.45
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (R)-3-O-Benzyl-2-O-<(diethylphosphonyl)methyl>-1-O-<(p-methoxyphenyl)diphenylmethyl>glycerol 在 palladium dihydroxide amberlyst-15 、 potassium carbonate 、 三乙胺 、 环己烯 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.5h， 生成 [(S)-2-(2,4-Dioxo-tetrahydro-pyrimidin-1-yl)-1-hydroxymethyl-ethoxymethyl]-phosphonic acid diethyl ester
  参考文献：
  名称：

  Synthesis and antiviral activity of the nucleotide analog (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cystosine

  摘要：

  The acyclic nucleotide analogue (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl] cytosine (2, HPMPC) was prepared on a multigram scale in 18% overall yield starting from (R)-2,3-O-isopropylideneglycerol. The key step in the nine-step synthetic route is coupling of cytosine with the side-chain derivative 8 which bears a protected phosphonylmethyl ether group. In vitro data showed that HPMPC has good activity against herpes simplex virus types 1 and 2, although it was 10-fold less potent than acyclovir [AVC, 9-[(2-hydroxyethoxy)methyl]guanine]. By comparison, HPMPC exhibited greater activity than ACV against a thymidine kinase deficient strain of HSV 1 and was more potent than ganciclovir [DHPG, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine] against human cytomegalovirus. In vivo, HPMPC showed exceptional potency against HSV 1 systemic infection in mice, having an ED50 of 0.1 mg/kg per day (ip) compared with 50 mg/kg per day for ACV. HPMPC was also more efficacious than ACV in the topical treatment of HSV 1 induced cutaneous lesions in guinea pigs.

  DOI：

  10.1021/jm00127a010
• 作为产物：
  描述：

  (R)-4-苄氧甲基-2,2-二甲基-1,3-二氧戊环 在 4-二甲氨基吡啶 、 硫酸 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 43.5h， 生成 (R)-3-O-Benzyl-2-O-<(diethylphosphonyl)methyl>-1-O-<(p-methoxyphenyl)diphenylmethyl>glycerol
  参考文献：
  名称：

  Synthesis and antiviral activity of the nucleotide analog (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cystosine

  摘要：

  The acyclic nucleotide analogue (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl] cytosine (2, HPMPC) was prepared on a multigram scale in 18% overall yield starting from (R)-2,3-O-isopropylideneglycerol. The key step in the nine-step synthetic route is coupling of cytosine with the side-chain derivative 8 which bears a protected phosphonylmethyl ether group. In vitro data showed that HPMPC has good activity against herpes simplex virus types 1 and 2, although it was 10-fold less potent than acyclovir [AVC, 9-[(2-hydroxyethoxy)methyl]guanine]. By comparison, HPMPC exhibited greater activity than ACV against a thymidine kinase deficient strain of HSV 1 and was more potent than ganciclovir [DHPG, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine] against human cytomegalovirus. In vivo, HPMPC showed exceptional potency against HSV 1 systemic infection in mice, having an ED50 of 0.1 mg/kg per day (ip) compared with 50 mg/kg per day for ACV. HPMPC was also more efficacious than ACV in the topical treatment of HSV 1 induced cutaneous lesions in guinea pigs.

  DOI：

  10.1021/jm00127a010

文献信息

• Drug. Future 1996, 21, 1003
  作者：

  DOI：——

  日期：——
• Nucleos. Nucleot. Nucl. 1989, 8, 923-926
  作者：

  DOI：——

  日期：——
• J. Med. Chem. 1989, 32, 1457-1463
  作者：

  DOI：——

  日期：——
• BRONSON, JOANNE J.;GHAZZOULI, ISMAIL;HITCHCOOCK, MICHAEL J. M.;WEBB, ROBE+, J. MED. CHEM., 32,(1989) N, C. 1457-1463
  作者：BRONSON, JOANNE J.、GHAZZOULI, ISMAIL、HITCHCOOCK, MICHAEL J. M.、WEBB, ROBE+

  DOI：——

  日期：——
• WEBB, ROBERT R.;WOS, JOHN A.;BRONSON, JOANNE J.;MARTIN, JOHN C., TETRAHEDRON LETT., 29,(1988) N 43, C. 5475-5478
  作者：WEBB, ROBERT R.、WOS, JOHN A.、BRONSON, JOANNE J.、MARTIN, JOHN C.

  DOI：——

  日期：——