4β-n-hexadecylsulfonamido-4'-tert-butyldimethylsilyloxy-4'-O-demethyl-4-desoxypodophyllotoxin | 692755-49-0

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 4β-n-hexadecylsulfonamido-4'-tert-butyldimethylsilyloxy-4'-O-demethyl-4-desoxypodophyllotoxin
• CAS: 692755-49-0
• 化学式: C₄₃H₆₇NO₉SSi
• 分子量: 802.158
• InChiKey: HERDIEIGHJKXKU-DJPKFGAVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.19
• 重原子数：
  55.0
• 可旋转键数：
  22.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  118.62
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  4β-n-hexadecylsulfonamido-4'-tert-butyldimethylsilyloxy-4'-O-demethyl-4-desoxypodophyllotoxin 在 Dowex 50 x 20-200 ion-exchange resin 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以96%的产率得到N-[(5S,5aS,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]hexadecane-1-sulfonamide
  参考文献：
  名称：

  Synthesis and Biological Activity of Sulfonamide Derivatives of Epipodophyllotoxin

  摘要：

  A series of novel 4beta-substituted sulfonamide derivatives of 4'-O-demethyl-4-desoxypodophyllotoxin has been synthesized. Their effects on human DNA topoisomerase II and, in some cases, on tubulin polymerization were evaluated. Compounds 8a, 8c, 8f, 8g, 8n, 8q, 8r, and 8s and the synthetic precursor 4 are potent topoisomerase II poisons that induce double-stranded breaks in DNA, with either improved or similar activity compared to etoposide. Only the amino precursor, compound 5, was slightly active in tubulin polymerization inhibition assays. We observed that the derivatives bearing an aromatic ring on the 4beta-sulfonamide substituent were either less cytotoxic or equivalent to the parent drug, while the sulfonamides containing an aliphatic side chain and the amino-sulfonamide derivatives, except 8d and 8g, exhibited increased cytoxicity compared to etoposide. In vivo, against the P388 leukemia and the A-549 orthotopic model of lung carcinoma, the most promising compounds were the morpholino- and the piperazino-containing sulfonamides derivatives 8r and 8s.

  DOI：

  10.1021/jm031117b
• 作为产物：
  描述：

  (5R,5aR,8aS,9S)-9-amino-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,5a,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(8H)-one 在 三乙烯二胺 、 咪唑 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 4β-n-hexadecylsulfonamido-4'-tert-butyldimethylsilyloxy-4'-O-demethyl-4-desoxypodophyllotoxin
  参考文献：
  名称：

  Synthesis and Biological Activity of Sulfonamide Derivatives of Epipodophyllotoxin

  摘要：

  A series of novel 4beta-substituted sulfonamide derivatives of 4'-O-demethyl-4-desoxypodophyllotoxin has been synthesized. Their effects on human DNA topoisomerase II and, in some cases, on tubulin polymerization were evaluated. Compounds 8a, 8c, 8f, 8g, 8n, 8q, 8r, and 8s and the synthetic precursor 4 are potent topoisomerase II poisons that induce double-stranded breaks in DNA, with either improved or similar activity compared to etoposide. Only the amino precursor, compound 5, was slightly active in tubulin polymerization inhibition assays. We observed that the derivatives bearing an aromatic ring on the 4beta-sulfonamide substituent were either less cytotoxic or equivalent to the parent drug, while the sulfonamides containing an aliphatic side chain and the amino-sulfonamide derivatives, except 8d and 8g, exhibited increased cytoxicity compared to etoposide. In vivo, against the P388 leukemia and the A-549 orthotopic model of lung carcinoma, the most promising compounds were the morpholino- and the piperazino-containing sulfonamides derivatives 8r and 8s.

  DOI：

  10.1021/jm031117b