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Development of Antitumor Compounds Led by Benzophenanthridine Compounds

以苯并菲啶化合物为主导的抗肿瘤化合物的开发

基本信息

批准号：
09557199
负责人：
HANAOKA Miyoji
金额：
$ 7.81万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

1. A simple and general synthesis of protoberberines and 13-methylprotoberberines via the same synthetic intermediates was newly developed. This method was applied to a new synthesis of protoberberine alkaloids.2. A novel biomimetic synthesis of benzophenanthridines form protoberberines through the enamine intermediates was developed. Benzophenanthridine alkaloids such as chelerythrine and nitidine were synthesized by this method.3. A new and simple synthesis of isocoumarins was developed employing palladium-catalyzed cyclization of o-alkenylbenzoic acids. This method was applied to a synthesis of a benzophenanthridine.4. Synthesis of hexahydrobenzophenanthridine alkaloids, corynoline and its stereoisomeric alkaloids from corresponding 13-methylprotoberberine alkaloid, corysamine was succeeded through a newly developed biomimetic route. An alkaloid having a unique substitution pattern, ambinine was totally synthesized by this method.5. A pyridoacridine skeleton was synthesized by a coupling reaction of quinoline derivative with phenylboric acid or phenyltin compound. Synthesis of antitumor marine alkaloids, cystodytin J and deplamine, was successfully realized by this method.6. We found a benzophenanthridine compound having high antitumor activity as well as activity against drug-resistant tumor cell.

1.本文报道了一种简便、通用的原小檗碱和13-甲基原小檗碱的合成方法。将该方法应用于原小檗碱生物碱的新合成.以原小檗碱为原料，通过烯胺中间体仿生合成了苯并菲啶。用此方法合成了白屈菜红碱和两面针碱等苯并菲啶类生物碱.以邻烯基苯甲酸为原料，钯催化环合反应合成了一系列异香豆素类化合物。将该方法应用于苯并菲啶的合成.以相应的13-甲基原小檗碱生物碱紫堇胺为原料，通过一条新的仿生路线合成了六氢苯并菲啶生物碱紫堇灵及其立体异构体生物碱。该方法完全合成了一种具有独特取代模式的生物碱--安比宁.通过喹啉衍生物与苯硼酸或苯锡化合物的偶联反应，合成了吡啶并吖啶骨架。利用该方法成功地合成了抗肿瘤海洋生物碱囊壁菌素J和去甲草胺.我们发现了一种苯并菲啶类化合物，它具有很高的抗肿瘤活性以及抗耐药肿瘤细胞的活性。