(1S,12R,15R,23S)-16-acetyl-12-methyl-3,11,14,16-tetrazahexacyclo[12.10.0.02,11.04,9.015,23.017,22]tetracosa-2,4,6,8,17,19,21-heptaene-10,13-dione | 216165-07-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (1S,12R,15R,23S)-16-acetyl-12-methyl-3,11,14,16-tetrazahexacyclo[12.10.0.02,11.04,9.015,23.017,22]tetracosa-2,4,6,8,17,19,21-heptaene-10,13-dione
• CAS: 216165-07-0
• 化学式: C₂₃H₂₀N₄O₃
• 分子量: 400.437
• InChiKey: WULWSUDZHHROKI-HATKXBDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  30
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  73.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,12R,15R,23S)-16-acetyl-12-methyl-3,11,14,16-tetrazahexacyclo[12.10.0.02,11.04,9.015,23.017,22]tetracosa-2,4,6,8,17,19,21-heptaene-10,13-dione 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 为溶剂， 反应 7.0h， 以16%的产率得到(12R,15S,23S)-16-acetyl-12-methyl-3,11,14,16-tetrazahexacyclo[12.10.0.02,11.04,9.015,23.017,22]tetracosa-1(24),2,4,6,8,17,19,21-octaene-10,13-dione
  参考文献：
  名称：

  立体和立体化学作用对MDR抑制剂N-乙酰氨基乙胺四环和六环片段的自由基溴化的影响

  摘要：

  几种四环3,5a，6,10b，11,11a-hexahydro-2 H -pyrazino [2'，1'-5,1] pyrrolo [2,3 - b ] indole-1,4- diones的溴化研究了自由基的条件。与相关吡咯并[2，3- b ]吲哚衍生物的文献数据相反，该反应通常发生在11a位而不是苄基10b位，然后消除，得到11,11a不饱和衍生物。在11a处位阻增加的化合物可提供B - C环芳构化衍生物。7,7a，10,14b，15,15a-hexahydroindolo [3“，2” -4'，5'] pyrrolo [2'，1'-3,4] -pyrazino [2,1-]的六环衍生物b] quinazoline-5,8-dione系统显示出与“无阻碍”四环相似的行为，从而导致天然MDR抑制剂N-乙酰乙二胺的不饱和类似物。还通过溴化四环系统的2-（邻叠氮苯甲酰基）衍生物，然后进行氮杂

  DOI：

  10.1016/s0040-4020(99)00886-8
• 作为产物：
  描述：

  (3R,5aR,10bS,11aS)-6-Acetyl-3-methyl-2,3,6,10b,11,11a-hexahydro-5aH-pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-1,4-dione 在 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 30.0h， 生成 (1S,12R,15R,23S)-16-acetyl-12-methyl-3,11,14,16-tetrazahexacyclo[12.10.0.02,11.04,9.015,23.017,22]tetracosa-2,4,6,8,17,19,21-heptaene-10,13-dione
  参考文献：
  名称：

  On the fate of the tryptophan stereocenter during the synthesis of hexacyclic analogues of N-acetylardeemin

  摘要：

  The reaction between 6-acetyl-3-alkyl-1-ethoxy-3,4,5a,6, 11,11a-hexahydro-10bH-pyrazino-[2 ',1 '-5,1]pyrrolo[2,3-b]indole-l,4-diones and anthranilic acid was studied from a stereochemical point of view. Various degrees of epimerization of the tryptophan and alanine stereocenters were observed in compounds with a cis relationship between their H-3 and H-11a hydrogen atoms, and stereochemistry was retained in the trans compounds. These observations are explained in terms of steric compression between the C-5=O, C-7-alkyl and C-8=O groups in the hexacyclic reaction products. Acylation at N-2 with o-azidobenzoyl chloride followed by an intramolecular aza Wittig reaction afforded the target 10-acetyl-5,7,8,9a, 10,14b, 15,15a-octahydroindolo[3 ",2 "-4 ',5 ']pyrrolo[2 ',1 '-3,4]pyrazino[2,1-b]quinazoline-5,8-diones with retention of all stereocenters. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(98)00307-3

文献信息

• Microwave-Assisted, Solvent-Free Synthesis of Several Quinazoline Alkaloid Frameworks
  作者：J. Menéndez、Pilar Cledera、Juan Sánchez、Esmeralda Caballero、Tamara Yates、Elena Ramírez、Carmen Avendaño、M. Ramos

  DOI：10.1055/s-2007-990818

  日期：2007.11

  Microwave irradiation leads to a considerable improvement of the cyclocondensation between anthranilic acid and lactim ethers derived from piperazine-2,5-diones in terms of reaction times, yields, and stereocenter integrity. This reaction has been used to prepare some derivatives of the pyrazino[2,1-b]quinazoline-3,6-dione system present in many quinazoline alkaloids. It could also be applied to the synthesis of compounds containing the complete hexacyclic ring system of the anti-MDR natural product N-acetyl­ardeemin, and other comprising the pentacyclic framework of circumdatin E. The microwave-assisted reaction was also much better than the thermal one when applied to a bis-lactim ether, leading to the corresponding pentacyclic pyrazino[2,1-b:5,4-b′]diquinazoline-8,16-dione in excellent yield.

  微波辐照显著改善了邻氨基苯甲酸与来自哌嗪-2,5-二酮的乳酰亚胺醚之间的环加成反应，在反应时间、产率和立体中心完整性方面均有显著提升。该反应已被用于制备多种喹唑啉生物碱中存在的吡嗪并[2,1-b]喹唑啉-3,6-二酮系统的衍生物。它还可以应用于合成含有抗多药耐药天然产物N-乙酰基阿德米宁的完整六环体系化合物，以及其他包含circumdatin E的五环框架的化合物。微波辅助反应在应用于双乳酰亚胺醚时也比热反应更为高效，得到了对应的五环吡嗪并[2,1-b:5,4-b′]双喹唑啉-8,16-二酮，产率极佳。