(+)-(1R,4S)-1-(3-indolylmethyl)-4-methyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione | 374114-82-6

• 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: (+)-(1R,4S)-1-(3-indolylmethyl)-4-methyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione
• 英文别名: (1R,4S)-1-(3-Indolylmethyl)-4-methyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione；ent-ardeemin fumiquinazoline；(1R,4S)-1-(1H-indol-3-ylmethyl)-4-methyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione
• CAS: 374114-82-6
• 化学式: C₂₁H₁₈N₄O₂
• 分子量: 358.4
• InChiKey: FHOFNRAVYAGXCQ-KPZWWZAWSA-N

物化性质

• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  77.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-(1R,4S)-1-(3-indolylmethyl)-4-methyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione 在 三氟乙酸 作用下， 反应 0.33h， 以72%的产率得到(+)-(5aR,8S,15bR,16aR)-8-methyl-5,5a,8,15b,16,16a-hexahydro-indolo[3'',2''-4',5']pyrrolo[2',1'-3,4]pyrazino[2,1-b]quinazoline-7,10-dione
  参考文献：
  名称：

  Influence of N(2)-substitution in the alkylation of (4S)-alkyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones

  摘要：

  1-Alkylation of O(3)-lactim, N(11)-azaenolate dilithium species derived from N(2)-H compounds 1a and 1b and the lithium azaenolates derived from the N(2)-phenyl and N(2)-(1-arylethyl) substituted compounds 2, 3 and 4 is studied. In 1 the trans-diastereoselectivity of 1-alkylation is controlled by 1,4-asyrnmetric induction, with some of these products prect.rsors of the ent-ardeemin framework. By contrast in compounds 2-4, the stabilization of the lithium azaenolate imposed by the phenyl substituent in 2, and the repulsive steric 1,2- interactions present in the initially formed 1,4-trans derivatives of 3 and 4, favou a C(1)-epimerization to the 1,4-cis isomers. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.07.034
• 作为产物：
  描述：

  D-色氨酸甲酯 在 三丁基膦 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 32.0h， 生成 (+)-(1R,4S)-1-(3-indolylmethyl)-4-methyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione
  参考文献：
  名称：

  3-Arylmethylpiperazine-2,5-diones 的区域选择性 N-酰化：(-)-Glyantrypine 和 (-)-Fumiquinazoline F 的短合成

  摘要：

  衍生自相应哌嗪-2,5-二酮的 2,5-双-O-三甲基甲硅烷基-3,6-二氢吡嗪中 3-芳基甲基取代基的折叠构象屏蔽了 N(1) 位，允许在相邻位置进行单酰化氮原子。利用这种区域选择性，开发了以 d-色氨酸甲酯为起始原料的 (-)-glyantrypine 和 (-)-fumiquinazoline F 的四步全合成方法。

  DOI：

  10.1055/s-2001-16785

文献信息

• Actions of Tryptophan Prenyltransferases Toward Fumiquinazolines and their Potential Application for the Generation of Prenylated Derivatives by Combining Chemical and Chemoenzymatic Syntheses
  作者：Peter Mai、Georg Zocher、Lena Ludwig、Thilo Stehle、Shu-Ming Li

  DOI：10.1002/adsc.201600064

  日期：2016.5.19

  different features of these enzymes toward ardeemin FQ analogues, regarding activity and prenylation position. Isolation and structural elucidation showed that 7‐DMATS catalyzed mainly regiospecific prenylation at C‐7, which is also observed for its natural substrate L‐tryptophan. Up to four prenylated derivatives were identified in the reaction mixtures of other enzymes. In total, 18 new prenylated

  d我中号乙基一个llyl吨ryptophan小号从焦磷酸二甲基色氨酸的吲哚环的各个位置异戊二烯基部分的ynthases（DMATSs）催化区域专一性转移反应。例如，FgaPT2，5- DMATS，并从7-DMATS曲霉真菌催化色氨酸异戊二烯化在C-4，C-5和C-7，而5-DMATS钪和6- DMATS萨从链霉菌菌株是色氨酸C- 5和C-6异戊烯基转移酶。在这项研究中，我们的目的是证明生产m的前体ardeemin fumiquinazoline（FQ）（1a）的异戊二烯基类似物的可能性。ULTI d地毯ř esistance（MDR）的出口泵抑制剂ardeemin，通过使用DMATSs。化学合成所有ardeemin FQ立体异构体，并用作DMATS酶分析的底物。生化研究表明，这些酶对ardeemin FQ类似物具有不同的活性和异戊烯化位置特征。分离和结构分析表明，7-DMATS主要在C-7
• Regioselective N-Acylation of 3-Arylmethylpiperazine-2,5-diones: Short Synthesis of (-)-Glyantrypine and (-)-Fumiquinazoline F
  作者：Fernando Hernández、Astrid Lumetzberger、Carmen Avendaño、Mónica Söllhuber

  DOI：10.1055/s-2001-16785

  日期：——

  The folded conformation of the 3-arylmethyl substituent in 2,5-bis-O-trimethylsilyl-3,6-dihydropyrazines derived from the corresponding piperazine-2,5-diones, shields the N(1)-position allowing monoacylation at the neighbouring nitrogen atom. This regioselectivity was used to develop a four-step total synthesis of (-)-glyantrypine and (-)-fumiquinazoline F starting from d-tryptophan methyl ester.

  衍生自相应哌嗪-2,5-二酮的 2,5-双-O-三甲基甲硅烷基-3,6-二氢吡嗪中 3-芳基甲基取代基的折叠构象屏蔽了 N(1) 位，允许在相邻位置进行单酰化氮原子。利用这种区域选择性，开发了以 d-色氨酸甲酯为起始原料的 (-)-glyantrypine 和 (-)-fumiquinazoline F 的四步全合成方法。
• Influence of N(2)-substitution in the alkylation of (4S)-alkyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones
  作者：Fernando Hernández、Viviana Morales、Félix L. Buenadicha、Mónica Söllhuber、Carmen Avendaño

  DOI：10.1016/j.tetasy.2004.07.034

  日期：2004.10

  1-Alkylation of O(3)-lactim, N(11)-azaenolate dilithium species derived from N(2)-H compounds 1a and 1b and the lithium azaenolates derived from the N(2)-phenyl and N(2)-(1-arylethyl) substituted compounds 2, 3 and 4 is studied. In 1 the trans-diastereoselectivity of 1-alkylation is controlled by 1,4-asyrnmetric induction, with some of these products prect.rsors of the ent-ardeemin framework. By contrast in compounds 2-4, the stabilization of the lithium azaenolate imposed by the phenyl substituent in 2, and the repulsive steric 1,2- interactions present in the initially formed 1,4-trans derivatives of 3 and 4, favou a C(1)-epimerization to the 1,4-cis isomers. (C) 2004 Elsevier Ltd. All rights reserved.