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

近年来，从海洋生物中分离得到了一系列具有结构相关性和生物活性的具有吡啶并[2，3，4-KL]吖啶或吡咯[2，3，4-KL]吖啶骨架的多环芳香族生物碱。在本研究项目中，我们完成了含亚氨基喹啉-苯醌结构的生物碱的合成，如11-羟基海藻毒素和鸟嘌呤甲素的全合成，并合成了吡咯并[2，3，4-KL]-吖啶(1)和苯并[b]吡咯[4，3，2-de][1，10]菲咯啉-8(11H)-酮(2)。以4-甲氧基-(或4-氯)-5，8-喹啉二酮与2-硝基-肉桂醛-二甲基肼的Diels-Alder杂化反应为关键步骤，合成了普拉激定A-C的骨架化合物：(A)4-甲氧基-(或4-氯)-5，8-喹啉二酮与2-硝基-肉桂醛-二甲基肼的杂化Diels-Alder反应；(B)以邻氨基苯乙酮和邻溴-苯二酚为原料合成了7-甲基苯并[b][1，10]菲咯啉-4(1H)-酮(3)。(C)以邻氨基苯乙酮和间溴代苯为原料，通过2-乙酰基吡咯并[2，3，4-KL]吖啶-1(2H)-酮(4)合成了与1具有相同骨架的吡咯并[2，3，4-KL]吖啶-1(2H)-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。

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.