Methyl (9S)-4-methoxy-11-oxo-2-oxa-10-azatricyclo<12.2.2.1^3,7>nonadeca-3,5,7(19),14,16,17-hexaene-9-carboxylate | 132539-23-2

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: Methyl (9S)-4-methoxy-11-oxo-2-oxa-10-azatricyclo<12.2.2.1^3,7>nonadeca-3,5,7(19),14,16,17-hexaene-9-carboxylate
• 英文别名: (9S)-2,11-dioxo-4-methoxy-9-methoxycarbonyl-10-azatricyclo[12.2.2.1^3,7]nonadeca-3,5,7(19),14,16,17-hexaene；Methyl (9S)-4-methoxy-11-oxo-2-oxa-10-azatricyclo[12.2.2.1^3,7]nonadeca-3,5,7(19),14,16,17-hexaene-9-carboxylate；Axbcceyicchjci-inizcteosa-；methyl (9S)-4-methoxy-11-oxo-2-oxa-10-azatricyclo[12.2.2.13,7]nonadeca-1(16),3,5,7(19),14,17-hexaene-9-carboxylate
• CAS: 132539-23-2
• 化学式: C₂₀H₂₁NO₅
• 分子量: 355.39
• InChiKey: AXBCCEYICCHJCI-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(4-碘苯基)丙酸 在 copper(I) bromide dimethylsulfide complex 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 Methyl (9S)-4-methoxy-11-oxo-2-oxa-10-azatricyclo<12.2.2.1^3,7>nonadeca-3,5,7(19),14,16,17-hexaene-9-carboxylate
  参考文献：
  名称：

  Intramolecular Ullmann condensation reaction: an effective approach to macrocyclic diaryl ethers

  摘要：

  The demonstration and definition of the scope of the intramolecular Ullmann condensation reaction suitable for use in macrocyclization reactions leading to 14-membered para- and metacyclophanes possessing a diaryl ether are detailed.

  DOI：

  10.1021/jo00005a020

文献信息

• Total synthesis of cycloisodityrosine, RA-VII, deoxybouvardin, and N29-desmethyl-RA-VII: Identification of the pharmacophore and reversal of the subunit functional roles
  作者：Dale L. Boger、Daniel Yohannes、Jiacheng Zhou、Michael A. Patane

  DOI：10.1021/ja00062a004

  日期：1993.5

  Full details of a concise total synthesis of RA-VII (1) and deoxybouvardin (2) are described based on the implementation of an effective intramolecular Ullmann reaction as the key macrocyclization reaction in the preparation of the elusive 14-membered cycloisodityrosine subunit (33) of the bicyclic hexapeptides. Subsequent coupling of 34 to tetrapeptide 17 and macrocyclization with C 2 -N 3 amide bond

  基于有效的分子内 Ullmann 反应作为制备难以捉摸的 14 元环异二酪氨酸亚基 (33) 的关键大环化反应的实施，描述了 RA-VII (1) 和脱氧布瓦丁 (2) 的简明全合成的全部细节的双环六肽。随后 34 与四肽 17 偶联以及大环化与 C 2 -N 3 酰胺键形成提供了 1 和 2。在解决有助于其抗肿瘤活性的药物的关键结构和构象特征的努力中，N 29 -去甲基-RA-制备了 VII 并详细说明了其化学、构象和初步生物学特性
• Total synthesis of deoxybouvardin and RA-VII: macrocyclization via an intramolecular Ullmann reaction
  作者：Dale L. Boger、Daniel Yohannes

  DOI：10.1021/ja00004a062

  日期：1991.2

  Ullmann condensation reaction for direct closure to the 14-membered diaryl ethers that have proven inaccessible or less accessible by alternative routes and the use of this key macrocyclization reaction in the total synthesis of RA-VII and deoxybouvardin

  我们详细介绍了实施分子内 Ullmann 缩合反应以直接封闭 14 元二芳基醚的成功研究，这些二芳基醚已证明无法通过替代途径或难以通过替代途径获得，以及在 RA-VII 的全合成中使用这种关键的大环化反应和脱氧布瓦丁
• Total Synthesis of an Antitumor Agent RA-VII via an Efficient Preparation of Cycloisodityrosine
  作者：Antony Bigot、Marie Elise Tran Huu Dau、Jieping Zhu

  DOI：10.1021/jo990432w

  日期：1999.8.1

  Details of efficient syntheses of (9S, 12S)-cycloisodityrosine (6) and a concise total synthesis of RA-VII(1) were described. An intramolecular SNAr-based cycloetherification reaction was employed as the key ring-closure step for construction of the illusive 14-membered m,p-cyclophane. Treatment of methyl N-[N-(tert-butyloxycarbonyl)-L(3-hydroxy-4-methoxyphenylalanyl)]-L-4-fluoro-3-nitrophenylalaninate ((9S,12S)-10) with potassium carbonate in DMSO at room temperature provided a mixture of two atropdiastereomers 20a and 20b in 75% yield that were transformed into cycloisodityrosine 6 in good overall yield. Furthermore, a size-selective ring-forming process was established for methyl N-[N-(tert-butyloxycarbonyl)-L-(3,4-dihydroxyphenlalanyl)]-L-4-fluoro-3- nitrophenylalaninate ((9S,12S)-11). Thus, cyclization of 11 (K2CO3, DMSO, rt), followed by in situ methylation, gave exclusively the 14-membered m,p-cyclphane 20a and 20b without competitive formation of the alternative 15-membered p,p-cyclophane. The selective ring-forming process allowed us to develop one of the shortest and the most efficient synthesis of cycloisodityrosine to date. Computational studies have shown that it was the elimination, but not the addition, step that determined the ring-size selectivity observed in the cyclization of substrate 11. Coupling of 6 with L-N-Boc-Ala (51) proceeded efficiently to provide the corresponding tripeptide 52 that, after removal of the N-Boc function, was allowed to react with another tripeptide 53 to afford the hexapeptide 50 in good overall yield. Saponification followed by liberation of amino function from 50 gave the seco-acid, whose cyclization (DPPA, DMF, NaHCO3) afforded the natural product RA-VII (1).