Studies on Synthesis and Biological Activities of Carbaeudistomins having Specific Anti viral Activities

具有特异性抗病毒活性的Carbaeudistomins的合成及生物活性研究

• 批准号: 06672128
• 负责人: KURIHARA Takushi
• 金额: $ 0.32万
• 依托单位: Osaka University of Pharmaceutical Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672128/
• 关键词: Antiviral Activity; Eudistomin; Carbaeudistomin; Oxathiazepine; Oxazepine; Structure-Activity Relationship; ユ-デイストミン; 12-カルバユーディストミン; マイゼンハイマー転位; 構造-活性相関

Tetracyclic eudistomins 1, which were isolated out of the colonial turnicate Eudistomin olivaceum, possessed very potent antiviral and antitumor activities.We have developed the synthesis of oxazepinopyridoindoles 2, which are corresponding to the carba analogs of natural eudistomins, via Meisenheimer rearrangement of azetopyridoindoles 4. For the structure activity relationship investigation of 1,12-carbaeudistomin analogs 3 were synthesized from 4 and their antiviral activities against influenza A and B virus, HSV-1, HSV-2, and human cytomegalovirus were evaluated. Among them, racemic 6-methoxy-12-carba- eudistomin 5 having beta-amino group has exhibited almost the same order activity as that of (-) -debromoeudistomin K,synthesized as a control compound. Also MNDO calculation showed that the conformation of the carbaeudistomins is very similar to that of natural eudistomins.These results clearly indicate that the oxazepine ring in the carbaeudistomins is equivalent to the oxathiazepine ring in the natural eudistomins for the antiviral activities.

四环eudistomins 1是从具有生物活性的Eudistomin olivaceum中分离得到的一类四环化合物，具有很强的抗病毒和抗肿瘤活性，我们通过Meisenheimer重排反应合成了一系列的氮杂吡啶并吲哚类化合物2，它们是天然eudistomins的碳类似物。为了研究1，12-carbaudistomin类似物的构效关系，从4合成了3，并评价了它们对甲型和B型流感病毒、HSV-1、HSV-2和人巨细胞病毒的抗病毒活性。其中，具有β-氨基的外消旋6-甲氧基-12-碳- eudistomin 5显示出与作为对照化合物合成的（-）-脱溴eudistomin K几乎相同的顺序活性。MNDO计算结果表明，careudistomins的构象与天然eudistomins的构象非常相似，表明careudistomins中的氧氮杂环与天然eudistomins中的氧硫氮杂环在抗病毒活性上是等价的。

项目成果

Takushi KURIHARA: "Meisenheimer Rearrangement of Azetopyridoindoles. VIII. Synthesis and Anitiviral Activities of 12-Carbaeudistomin Analogs." Chem. Pharm. Bull.44. (1996)

Takushi KURIHARA：“Meisenheimer 重排氮杂吡啶并吲哚。VIII. 12-Carbaeudistomin 类似物的合成和抗病毒活性。”

Takushi KURIHARA: "Meisenheimer Rearrangement of Azetopyridoindoles. VIII. Synthesis and Antiviral Activities of 12-Carbaeudistomin Analogs" Chem. Pharm. Bull.44. (1996)

Takushi KURIHARA：“Meisenheimer 重排 Azetopyridoindoles。VIII. 12-Carbaeudistomin 类似物的合成和抗病毒活性”Chem。

Takushi KURIHARA: "Meisenheimer Rearrangement of Azetopyridoindoles. VI. Synthesis of 12-Carbaeudistomin and Related Compounds" Chem. Pharm. Bull.42. 475-480 (1994)

Takushi KURIHARA：“Meisenheimer 重排氮杂吡啶并吲哚。VI。12-Carbaeudistomin 和相关化合物的合成”Chem。

Takushi KURIHARA: "Meisenheimer Rearrangement of Azetopyridoindoles. VII. Ring expansion of 2-Phenylazeto[1′, 2′: 1,2]pyrido[3,4-b]indoles by Oxidation with MCPBA" Chem. Pharm. Bull.43. 1089-1095 (1995)

Takushi KURIHARA：“Meisenheimer 重排 Azetopyridoindoles。VII. 通过 MCPBA 氧化实现 2-Phenylazeto[1, 2: 1,2]pyrido[3,4-b]indoles 环扩展”Chem.43。 1089-1095 (1995)

T.Kurihara, Y.Sakamoto, H.Ohishi, N.Kawabata, S.Harusawa, and R.Yoneda: "Meisenheimer Rearrangement of Azetopyridoindoles. VI.Synthesis of 12-carbaeudistomin and Related Compounds" Chem.Pharm.Bull.42 (3). 475-480 (1994)

T.Kurihara、Y.Sakamoto、H.Ohishi、N.Kawabata、S.Harusawa 和 R.Yoneda：“Meisenheimer 重排 Azetopyridoindoles。VI.12-carbaeudistomin 和相关化合物的合成”Chem.Pharm.Bull.42（