rac-1-S-octadecyl-3-O-(tert-butyldimethylsilyl)-1-thioglycerol | 94478-27-0

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: rac-1-S-octadecyl-3-O-(tert-butyldimethylsilyl)-1-thioglycerol
• 英文别名: t-butyldimethylsilyloxy-1 octadecylthio-3 propanol-2；1-[Tert-butyl(dimethyl)silyl]oxy-3-octadecylsulfanylpropan-2-ol
• CAS: 94478-27-0
• 化学式: C₂₇H₅₈O₂SSi
• 分子量: 474.908
• InChiKey: QRDCGNZMQYLWMW-UHFFFAOYSA-N

物化性质

• 沸点：
  530.6±40.0 °C(Predicted)
• 密度：
  0.899±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.36
• 重原子数：
  31
• 可旋转键数：
  23
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  54.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  rac-1-S-octadecyl-3-O-(tert-butyldimethylsilyl)-1-thioglycerol 在 吡啶 、 四丁基氟化铵 、 水 、 溶剂黄146 、 三乙胺 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 31.0h， 生成
  参考文献：
  名称：

  Nucleoside conjugates. 13. Synthesis and antitumor activity of 1-.beta.-D-arabinofuranosylcytosine conjugates of thioether lipids with improved water solubility

  摘要：

  A series of ara-CDP-rac-1-S-alkyl-2-0-acyl-1-thioglycerols (3-12), analogues of highly active Cytoros2 (1), was prepared, and solubility, lipophilicity, and structure-activity relationships of these conjugates were investigated. The conjugates with sn-1 alkyl (C14) and the sn-2 fatty acyl (>C16) were sparingly soluble. The latter formed micelles upon sonication. Conjugate 7 containing the sn-1 tetradecyl and the sn-2 palmitoyl (C16) groups formed micelles by both sonication and shaking. The partition coefficients (1-octanol/PBS) of the water-soluble conjugates were about 20 times greater than that of ara-C. The water-insoluble showed a more than 40 times increase. A single dose of the micelle-forming conjugates 7 and 10 produced a significant increase in life span (ILS >421 %) with 50 % long-term survivors (>45 days) in mice bearing ip-implanted L1210 lymphoid leukemia. These results were comparable to those of previous micelle-forming conjugate 1 (Cytoros). In contrast, the water-soluble conjugates at single doses were less effective (ILS 81-386% with 0-33% long-term survivors). However, three divided doses of the water-soluble conjugates were found to be as effective as a single dose of micellar solution of the water-insoluble. The results indicate that conjugate 7 and most of the water-soluble derivatives warrant further investigation.

  DOI：

  10.1021/jm00064a012
• 作为产物：
  描述：

  硬脂基溴 在 咪唑 、 氢氧化钾 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 生成 rac-1-S-octadecyl-3-O-(tert-butyldimethylsilyl)-1-thioglycerol
  参考文献：
  名称：

  Nucleoside conjugates. 11. Synthesis and antitumor activity of 1-.beta.-D-arabinofuranosylcytosine and cytidine conjugates of thioether lipids

  摘要：

  Five 1-beta-D-arabinofuranosylcytosine conjugates and two cytidine conjugates of thioether lipids (1-S-alkylthioglycerols) linked by a pyrophosphate diester bond have been prepared and their antitumor activity against an ara-C2 sensitive (L1210/0) and two ara-C resistant L1210 lymphoid leukemia sublines in mice were evaluated. These prodrugs of ara-C include ara-CDP-rac-1-S-hexadecyl-2-O-palmitoyl-1-thioglycerol (8a), ara-CDP-rac-1-S-octadecyl-2-O-palmitoylthioglycerol (8b), and ara-CDP-rac-1-S-octadecyl-2-O-methyl(or -ethyl, -hexadecyl)thioglycerols (8c-e). The cytidine conjugates include CDP-rac-1-S-octadecyl-2-O-palmitoyl(or -methyl)- 1-thioglycerols (9a and 9b). Sonicated solutions of the conjugates existed in the form of micellar disks (size 0.01-0.04 microns). Single doses (200-400 mg/kg) of 8a and 8b produced significant increase in life span (257-371%) in mice bearing ip implanted L1210/0 leukemia. In contrast, conjugates 8c-e were less effective (ILS 19-75%) and cytidine conjugates (9a and 9b) were ineffective. Even though 8a and 8b were found to be curative in a high percentage of mice bearing ip implanted partially ara-C resistant L1210 subline [L1210/ara-C(I)], they were completely ineffective against deoxycytidine kinase deficient ara-C resistant L1210 subline [L1210/ara-C(II)]. However, the present results, together with the previous, demonstrate that 8a and 8b are promising new prodrugs of ara-C with improved efficacy.

  DOI：

  10.1021/jm00167a016

文献信息

• Garrigues, Bernard; Bertrand, Guy; Frehel, Daniel, Phosphorus and Sulfur and the Related Elements, 1984, vol. 21, p. 171 - 176
  作者：Garrigues, Bernard、Bertrand, Guy、Frehel, Daniel、Maffrand, Jean-Pierre

  DOI：——

  日期：——
• Nucleoside conjugates. 11. Synthesis and antitumor activity of 1-.beta.-D-arabinofuranosylcytosine and cytidine conjugates of thioether lipids
  作者：Chung Il Hong、Alan J. Kirisits、Alexander Nechaev、David J. Buchheit、Charles R. West

  DOI：10.1021/jm00167a016

  日期：1990.5

  Five 1-beta-D-arabinofuranosylcytosine conjugates and two cytidine conjugates of thioether lipids (1-S-alkylthioglycerols) linked by a pyrophosphate diester bond have been prepared and their antitumor activity against an ara-C2 sensitive (L1210/0) and two ara-C resistant L1210 lymphoid leukemia sublines in mice were evaluated. These prodrugs of ara-C include ara-CDP-rac-1-S-hexadecyl-2-O-palmitoyl-1-thioglycerol (8a), ara-CDP-rac-1-S-octadecyl-2-O-palmitoylthioglycerol (8b), and ara-CDP-rac-1-S-octadecyl-2-O-methyl(or -ethyl, -hexadecyl)thioglycerols (8c-e). The cytidine conjugates include CDP-rac-1-S-octadecyl-2-O-palmitoyl(or -methyl)- 1-thioglycerols (9a and 9b). Sonicated solutions of the conjugates existed in the form of micellar disks (size 0.01-0.04 microns). Single doses (200-400 mg/kg) of 8a and 8b produced significant increase in life span (257-371%) in mice bearing ip implanted L1210/0 leukemia. In contrast, conjugates 8c-e were less effective (ILS 19-75%) and cytidine conjugates (9a and 9b) were ineffective. Even though 8a and 8b were found to be curative in a high percentage of mice bearing ip implanted partially ara-C resistant L1210 subline [L1210/ara-C(I)], they were completely ineffective against deoxycytidine kinase deficient ara-C resistant L1210 subline [L1210/ara-C(II)]. However, the present results, together with the previous, demonstrate that 8a and 8b are promising new prodrugs of ara-C with improved efficacy.
• HONG, CHUNG IL;KIRISITS, ALAN J.;NECHAEV, ALEXANDER;BUCHHEIT, DAVID J.;WE+, J. MED. CHEM., 33,(1990) N, C. 1380-1386
  作者：HONG, CHUNG IL、KIRISITS, ALAN J.、NECHAEV, ALEXANDER、BUCHHEIT, DAVID J.、WE+

  DOI：——

  日期：——
• BERTRAND, G.;GARRIGUES, B.;MAFFRAND, J.
  作者：BERTRAND, G.、GARRIGUES, B.、MAFFRAND, J.

  DOI：——

  日期：——
• BERTRAND, G.;GARRIGUES, B.;MAFFRAND, J. -P.
  作者：BERTRAND, G.、GARRIGUES, B.、MAFFRAND, J. -P.

  DOI：——

  日期：——