aplaminal | 1005010-20-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: aplaminal
• 英文别名: methyl (1R,5S)-6-(4-methoxycarbonylphenyl)-8-methyl-4-oxo-3,6,8-triazabicyclo[3.2.1]octane-5-carboxylate
• CAS: 1005010-20-7
• 化学式: C₁₆H₁₉N₃O₅
• 分子量: 333.344
• InChiKey: KSNSGYBJVDSZCB-WBMJQRKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  88.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  dimethyl (4R)-4-(aminomethyl)-1-(4-methoxycarbonylphenyl)-3-methylimidazolidine-2,2-dicarboxylate 在 三甲基铝 作用下， 以 正己烷 、 甲苯 为溶剂， 反应 21.0h， 以66%的产率得到aplaminal
  参考文献：
  名称：

  Total Synthesis of (−)-Aplaminal

  摘要：

  The total synthesis and assignment of absolute configuration of (-)-aplaminal (1), a cytotoxic metabolite from a sea hare possessing a triazobicyclo[3.2.1]octane skeleton, has been achieved. The synthesis entailed condensation of a monoprotected diamine (3) with dimethyl 2-oxomalonate (4) to generate the imidazolidine core (2). Introduction of the third nitrogen via Mitsunobu activation and azide displacement, followed by reduction and lactam formation (AIMe(3)), furnished (-)-aplaminal (1). Overall, the synthesis entailed 9 steps and proceeded in 19% overall yield.

  DOI：

  10.1021/ol801794f

文献信息

• Total synthesis of (−)-aplaminal by Buchwald–Hartwig cross-coupling of an aminal
  作者：Takayuki Ohyoshi、Kei Akemoto、Ayaka Taniguchi、Takuma Ishihara、Hideo Kigoshi

  DOI：10.1039/c9nj04743c

  日期：——

  The concise total synthesis of an unusual alkaloid, aplaminal, has been accomplished. The synthetic feature is the Buchwald–Hartwig cross-coupling between a novel triazabicyclo[3.2.1]octane core and an aromatic bromide. The practicality of our approach provides aplaminal analogs and preliminary structure–cytotoxicity relationships of an aromatic moiety were achieved.

  已经完成了不寻常的生物碱，铝绿蛋白的简明全合成。合成特征是新型三氮杂双环[3.2.1]辛烷核与芳香族溴化物之间的布赫瓦尔德-哈特维格交叉偶联。我们的方法的实用性提供了铝白蛋白类似物，并实现了芳香族部分的初步结构-细胞毒性关系。
• Bioinspired Total Synthesis and Structure-Activity Relationship Studies on Aplaminal
  作者：Takayuki Ohyoshi、Yiwen Zhao、Kei Akemoto、Takuma Ishihara、Ayaka Taniguchi、Menghua Zhang、Hideo Kigoshi

  DOI：10.1246/bcsj.20220149

  日期：2022.8.15

  The total synthesis of aplaminal having the unique triazabicyclo[3.2.1]octane skeleton was accomplished by using biomimetic oxidative cyclization as a key reaction. This total synthesis enabled us to prepare aplaminal analogs with a variety of substituents at para-position in the aromatic ring. We found that an electron-donating group at the para-position enhances cytotoxicity and a hydrogen bond donor

  以仿生氧化环化为关键反应，完成了具有独特的三氮杂双环[3.2.1]辛烷骨架的aplaminal的全合成。这种全合成使我们能够制备在芳环对位具有多种取代基的aplaminal类似物。我们发现对位的给电子基团增强细胞毒性，对位的氢键供体适合细胞毒性。
• Total Synthesis of (−)-Aplaminal
  作者：Amos B. Smith、Zhuqing Liu

  DOI：10.1021/ol801794f

  日期：2008.10.2

  The total synthesis and assignment of absolute configuration of (-)-aplaminal (1), a cytotoxic metabolite from a sea hare possessing a triazobicyclo[3.2.1]octane skeleton, has been achieved. The synthesis entailed condensation of a monoprotected diamine (3) with dimethyl 2-oxomalonate (4) to generate the imidazolidine core (2). Introduction of the third nitrogen via Mitsunobu activation and azide displacement, followed by reduction and lactam formation (AIMe(3)), furnished (-)-aplaminal (1). Overall, the synthesis entailed 9 steps and proceeded in 19% overall yield.