(8Z,13Z)-(3S,4R,5R,10S,11R,12S)-5,11-Bis-(4-methoxy-benzyloxy)-16-((2S,3S,4S,5R,6R)-6-methoxy-4-methoxymethoxy-3,5-dimethyl-tetrahydro-pyran-2-yl)-2,4,10,12-tetramethyl-hexadeca-8,13-dien-3-ol | 565229-93-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (8Z,13Z)-(3S,4R,5R,10S,11R,12S)-5,11-Bis-(4-methoxy-benzyloxy)-16-((2S,3S,4S,5R,6R)-6-methoxy-4-methoxymethoxy-3,5-dimethyl-tetrahydro-pyran-2-yl)-2,4,10,12-tetramethyl-hexadeca-8,13-dien-3-ol
• CAS: 565229-93-8
• 化学式: C₄₆H₇₂O₉
• 分子量: 769.072
• InChiKey: HRVKHASAZAQCLN-ZFOANTNSSA-N

物化性质

• 沸点：
  777.2±60.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.41
• 重原子数：
  55.0
• 可旋转键数：
  25.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  94.07
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (8Z,13Z)-(3S,4R,5R,10S,11R,12S)-5,11-Bis-(4-methoxy-benzyloxy)-16-((2S,3S,4S,5R,6R)-6-methoxy-4-methoxymethoxy-3,5-dimethyl-tetrahydro-pyran-2-yl)-2,4,10,12-tetramethyl-hexadeca-8,13-dien-3-ol 在 碳酸氢钠 、 戴斯-马丁氧化剂 、 溶剂黄146 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.5h， 生成 carbamic acid, (1S,2S,3R,6Z,8S,9S,10S,11Z)-3,9-dihydroxy-14-[(2S,3R,4S,5R)-4-methoxymethoxy-3,5-dimethyl-6-oxotetrahydropyran-2-yl]-2,8,10-trimethyl-1-(1-methylpenta-2,4-dienyl)tetradeca-6,11-dienyl ester
  参考文献：
  名称：

  Simplified Discodermolide Analogues:  Synthesis and Biological Evaluation of 4-epi-7-Dehydroxy-14,16-didemethyl-(+)-discodermolides as Microtubule-Stabilizing Agents

  摘要：

  Several novel analogues of (+)-discodermolide were synthesized via a convergent strategy that used Wittig reactions to append left and right side chains to a central scaffold and then tested for biological activity. Three of the analogues in the 4-epi-7-dehydroxy-14,16-didemethyl series, 6a-c, had interesting actions. The C3-methoxymethyl ether analogue 6b was more active in antiproliferative cell-based assays as well as in hypernucleation and paclitaxel site competition assays with isolated tubulin than the other analogues, including 6a, which contained a free hydroxyl group at the C3 position. The biological results validated the initial hypothesis that the C7 hydroxy group and the C14 and C16 methyl groups of (+)-discodermolide could be deleted without undermining activity. Although less potent than (+)-discodermolide and paclitaxel, compounds 6b and 6c both showed properties unique to (+)-discodermolide. These properties, particularly the capacity to cause hypernucleation of isolated tubulin at lower temperature than paclitaxel, as well as stabilizing preformed microtubules to cold disassembly, are considered mechanistically superior to those of paclitaxel. Other variations in the right and left sides of the discodermolide scaffold revealed additional structure/activity information.

  DOI：

  10.1021/jm0204136
• 作为产物：
  描述：

  4-甲氧基苯甲醛二甲缩醛 在 咪唑 、 四丁基氟化铵 、 碘 、 sodium hexamethyldisilazane 、 三氧化硫吡啶 、 4-甲基苯磺酸吡啶 、 二异丁基氢化铝 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 二甲基亚砜 、 苯 为溶剂， 反应 56.32h， 生成 (8Z,13Z)-(3S,4R,5R,10S,11R,12S)-5,11-Bis-(4-methoxy-benzyloxy)-16-((2S,3S,4S,5R,6R)-6-methoxy-4-methoxymethoxy-3,5-dimethyl-tetrahydro-pyran-2-yl)-2,4,10,12-tetramethyl-hexadeca-8,13-dien-3-ol
  参考文献：
  名称：

  Simplified Discodermolide Analogues:  Synthesis and Biological Evaluation of 4-epi-7-Dehydroxy-14,16-didemethyl-(+)-discodermolides as Microtubule-Stabilizing Agents

  摘要：

  Several novel analogues of (+)-discodermolide were synthesized via a convergent strategy that used Wittig reactions to append left and right side chains to a central scaffold and then tested for biological activity. Three of the analogues in the 4-epi-7-dehydroxy-14,16-didemethyl series, 6a-c, had interesting actions. The C3-methoxymethyl ether analogue 6b was more active in antiproliferative cell-based assays as well as in hypernucleation and paclitaxel site competition assays with isolated tubulin than the other analogues, including 6a, which contained a free hydroxyl group at the C3 position. The biological results validated the initial hypothesis that the C7 hydroxy group and the C14 and C16 methyl groups of (+)-discodermolide could be deleted without undermining activity. Although less potent than (+)-discodermolide and paclitaxel, compounds 6b and 6c both showed properties unique to (+)-discodermolide. These properties, particularly the capacity to cause hypernucleation of isolated tubulin at lower temperature than paclitaxel, as well as stabilizing preformed microtubules to cold disassembly, are considered mechanistically superior to those of paclitaxel. Other variations in the right and left sides of the discodermolide scaffold revealed additional structure/activity information.

  DOI：

  10.1021/jm0204136