ethyl (R)-4-tert-butoxycarbonylamino-5-(triphenylmethylthio)-pentanonate | 1585181-22-1

• 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: ethyl (R)-4-tert-butoxycarbonylamino-5-(triphenylmethylthio)-pentanonate
• 英文别名: ethyl (R)-4-tert-butoxycarbonylamino-5-(triphenylmethylthio)pentanoate
• CAS: 1585181-22-1
• 化学式: C₃₁H₃₇NO₄S
• 分子量: 519.705
• InChiKey: HCMWPNXRQDLBLK-HHHXNRCGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.95
• 重原子数：
  37.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  64.63
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl (R)-4-tert-butoxycarbonylamino-5-(triphenylmethylthio)-pentanonate 在 2,6-二甲基吡啶 、 盐酸 、 四(三苯基膦)钯 、 三氟甲磺酸酐 、 三氟甲磺酸三甲基硅酯 、 ammonium acetate 、 水 、 2-bromo-1-ethylpyridin-1-ium tetrafluoroborate 、 potassium carbonate 、 二乙胺 、 N,N-二异丙基乙胺 、 ((3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V) 、 N-甲基苯胺 、 三苯基氧化膦 、 sodium hydroxide 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 30.0h， 生成 apratoxin S4
  参考文献：
  名称：

  Improved Total Synthesis and Biological Evaluation of Potent Apratoxin S4 Based Anticancer Agents with Differential Stability and Further Enhanced Activity

  摘要：

  Apratoxins are cytotoxic natural products originally isolated from marine cyanobacteria that act by preventing cotranslational translocation early in the secretory pathway to downregulate receptor levels and inhibit growth factor secretion, leading to potent antiproliferative activity. Through rational design and total synthesis of an apratoxin A/ E hybrid, apratoxin S4 (1a), we have previously improved the antitumor activity and tolerability in vivo. Compound la and newly designed analogues apratoxins S7-S9 (1b-d), with various degrees of methylation at C34 (1b,c) or epimeric configuration at C30 (1d), were efficiently synthesized utilizing improved procedures. Optimizations have been applied to the synthesis of key intermediate aldehyde 7 and further include the application of Leighton's silanes and modifications of Kelly's methods to induce thiazoline ring formation in other crucial steps of the apratoxin synthesis. Apratoxin S9 (1d) exhibited increased activity with subnanomolar potency. Apratoxin S8 (lc) lacks the propensity to be deactivated by dehydration and showed efficacy in a human HCT116 xenograft mouse model.

  DOI：

  10.1021/jm4019965
• 作为产物：
  描述：

  N-叔丁氧羰基-S-三苯甲基-L-半胱氨酸 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 36.5h， 生成 ethyl (R)-4-tert-butoxycarbonylamino-5-(triphenylmethylthio)-pentanonate
  参考文献：
  名称：

  Improved Total Synthesis and Biological Evaluation of Potent Apratoxin S4 Based Anticancer Agents with Differential Stability and Further Enhanced Activity

  摘要：

  Apratoxins are cytotoxic natural products originally isolated from marine cyanobacteria that act by preventing cotranslational translocation early in the secretory pathway to downregulate receptor levels and inhibit growth factor secretion, leading to potent antiproliferative activity. Through rational design and total synthesis of an apratoxin A/ E hybrid, apratoxin S4 (1a), we have previously improved the antitumor activity and tolerability in vivo. Compound la and newly designed analogues apratoxins S7-S9 (1b-d), with various degrees of methylation at C34 (1b,c) or epimeric configuration at C30 (1d), were efficiently synthesized utilizing improved procedures. Optimizations have been applied to the synthesis of key intermediate aldehyde 7 and further include the application of Leighton's silanes and modifications of Kelly's methods to induce thiazoline ring formation in other crucial steps of the apratoxin synthesis. Apratoxin S9 (1d) exhibited increased activity with subnanomolar potency. Apratoxin S8 (lc) lacks the propensity to be deactivated by dehydration and showed efficacy in a human HCT116 xenograft mouse model.

  DOI：

  10.1021/jm4019965