ピロロ〔2,3,4-kl]アクリジン骨格を有する生理活性天然物の合成

吡咯并[2,3,4-kl]吖啶骨架生物活性天然产物的合成

• 批准号: 10672004
• 负责人: KITAHARA Yoshiyasu
• 金额: $ 0.83万
• 依托单位: MEIJI PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672004/
• 关键词: pyrroloacridine; alkaloid; polycyclic heteroaromatic compound; marine natural product; total synthesis; 芳香族化合物

In recent years a series of structurally related and biologically active polycyclic aromatic alkaloids possessing pyrido [2,3,4-kl] acridine or pyrrolo [2,3,4-kl] acridine skeleton have been isolated from marine organisms. We achieved synthesis of the alkaloids including iminoquinoline-quinone structure, e.g. 11-hydroxyascididemin and kuanoniamine A.In this research project we have studied total synthesis of meridine and cystodamine, and synthesis of pyrrolo [2,3,4-kl]- acridine (1) and benzo [b] pyrrolo [4,3,2-de][1,10] phenanthrolin-8 (11H)-one (2), a common skeleton of plakinidine A-C.(a) Meridine and cystodamine were synthesized by using hetero Diels-Alder reaction between 4-methoxy-(or 4-chloro-) 5,8-quinolinedione and 2-nitrocinnamaldehyde dimethylhydrazone as a key step.(b) 7-methylbenzo [b][1,10] phenanthrolin-4 (1H)-one (3) was obtained from o-aminoacetophenone and o-bromonitrobenzene. However we found that synthesis of 2 from 3 will be difficult.(c) Pyrrolo [2,3,4-kl] acridin-1 (2H)-one possessing the same skeleton as 1 was synthesized from o-Aminoacetophenone and m-bromonitrobenzene via 2-acetylpyrrolo [2,3,4-kl] acridin-1 (2H)-one (4). 6,11-dihydrobenzo [b] pyrrolo [4,3,2-de][1,10] phenanthroline-5, 8-dione possessing the same skeleton as 2 was synthesized from 4.

近年来，从海洋生物中分离出一系列结构相似、具有生物活性的吡啶并[2，3，4-kl]吖啶或吡咯并[2，3，4-kl]吖啶骨架的多环芳香族生物碱。本课题研究了meridine和cystodamine的全合成，吡咯并[2，3，4-kl]-吖啶（1）和苯并[B]吡咯并[4，3，2-de][1，10]菲咯啉-8（11 H）-酮（2）的合成，普拉基尼定A-C的共同骨架。(a)以4-甲氧基-（或4-氯-）-5，8-喹啉二酮与2-硝基肉桂醛二甲腙的杂Diels-Alder反应为关键步骤，合成了美利定和胱丹明。(b)以邻氨基苯乙酮和邻溴硝基苯为原料合成了7-甲基苯并[B][1，10]菲咯啉-4（1H）-酮（3）。然而，我们发现从3合成2将是困难的。(c)以邻氨基苯乙酮和间溴硝基苯为原料，经2-乙酰基吡咯并[2，3，4-kl]吖啶-1（2 H）-酮（4）合成了与1具有相同骨架的吡咯并[2，3，4-kl]吖啶-1（2 H）-酮。以4为原料合成了与2具有相同骨架的6，11-二氢苯并[B]吡咯并[4，3，2-de][1，10]菲咯啉-5，8-二酮。

项目成果

北原嘉泰,久保陽徳 他: "Synthesis of Meridine, Cystodamine, and Related Compounds Including Iminoquinolinequinone Structure"Tetrahedron Letters. 54. 8421-8432 (1998)

Yoshiyasu Kitahara、Yoshinori Kubo 等：“Meridine、Cystodamine 和包括亚氨基喹啉醌结构的相关化合物的合成”Tetrahedron Letters 54. 8421-8432 (1998)。

Kitahara, Y. ; Tamura, F. ; Nishimura, M. ; Kubo, A.: "Synthesis of Meridine, Cystodamine, and Related Compounds Including Iminoquinolinequinone Structure"Tetrahedron Letters. 54 (29). 8421-8432 (1998)

北原，Y.；