Development of Antitumor Compounds Led by Benzophenanthridine Compounds

1.通过相同的合成中间体，建立了一种简单、通用的合成原黄连素和13-甲基原黄连素的方法。将该方法应用于原黄连素生物碱的新合成。提出了一种以原小檗碱为原料，通过烯胺类中间体仿生合成苯并菲的新方法。用该方法合成了白屈菜红碱、两面针碱等苯并菲并菲生物碱。利用钯催化邻烯基苯甲酸环合反应合成了一种新的、简单的异香豆素类化合物。将该方法应用于苯并菲并菲的合成。通过一条新的仿生路线成功地从相应的13-甲基原小檗碱生物碱、科里沙明合成了六氢苯并菲并菲生物碱、科林诺林及其立体异构体生物碱。用该方法合成了一种具有独特取代模式的生物碱--氨宾。通过喹啉类化合物与苯基硼酸或苯基锡化合物的偶联反应，合成了一种吡哆吖啶骨架化合物。利用该方法成功地合成了抗肿瘤海洋生物碱--半胱氨酸J和去甲胺。我们发现了一种具有较高抗肿瘤活性和抗耐药肿瘤细胞活性的苯并菲并吡啶类化合物。

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.