3-(4-Methylphenyl)sulfonyl-4-propan-2-yl-1,3,2-oxazaborolidin-5-one | 222990-75-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4-Methylphenyl)sulfonyl-4-propan-2-yl-1,3,2-oxazaborolidin-5-one
• 英文别名: 3-(4-methylphenyl)sulfonyl-4-propan-2-yl-1,3,2-oxazaborolidin-5-one
• CAS: 222990-75-2
• 化学式: C₁₂H₁₆BNO₄S
• 分子量: 281.14
• InChiKey: LLAUKPDGEHPLNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.83
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-对甲苯磺酰基-D-缬氨酸 在 硼烷四氢呋喃络合物 作用下， 以 二氯甲烷 为溶剂， 生成 3-(4-Methylphenyl)sulfonyl-4-propan-2-yl-1,3,2-oxazaborolidin-5-one
  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
• 作为试剂：
  描述：

  4-羟基-5,5-二甲基-2-己酮 在 咪唑 、 titanium(IV) isopropylate 、 盐酸 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 三氟甲磺酸 、 3-(4-Methylphenyl)sulfonyl-4-propan-2-yl-1,3,2-oxazaborolidin-5-one 、 N-对甲苯磺酰基-D-缬氨酸 、 硼烷 、 potassium tert-butylate 、 ammonium acetate 、 四丁基氟化铵 、 水 、 三甲基铝 、 copper(l) cyanide 、 四氯化钛 、 二异丁基氢化铝 、 potassium carbonate 、 甲基磺酰氯 、 三乙胺 、 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 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 lithium hydroxide 、 锌 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醚 、 二氯甲烷 、 六氯-1,3-丁二烯 、 水 、 二甲基亚砜 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 58.67h， 生成 pyrrolidine-1,2-dicarboxylic acid (2S)-2-{(1S,3S,5S)-6-[(5S)-5-(2-allyloxycarbonylethyl)-4,5-dihydro-thiazol-2-yl]-1-tert-butyl-3,6-dimethyl-5-hydroxyhept-1-yl}ester 1-(9H-fluoren-9-ylmethyl)ester
  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

文献信息

• Improved Total Synthesis and Biological Evaluation of Potent Apratoxin S4 Based Anticancer Agents with Differential Stability and Further Enhanced Activity
  作者：Qi-Yin Chen、Yanxia Liu、Weijing Cai、Hendrik Luesch

  DOI：10.1021/jm4019965

  日期：2014.4.10

  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.