Development of practical supply of isoquinoline marine natural products to designate the creation of the new anticancer agents

作为我们在从泰国海洋动物中分离和表征生物活性化合物的过程中寻找新的抗癌代谢物的一部分，我们成功地发现了蓝色海绵Xestospongia sp.。本文报道了用氰化钾在甲醇缓冲溶液中预处理海洋动物的主要产物雷那霉素M的分离和结构鉴定。这是第一个从海洋来源供应克级雷尼霉素类产品的例子。雷尼霉素M对多种肿瘤细胞具有较强的细胞毒活性，易转化为约鲁霉素和雷尼霉素J。我们发现，氧化降解jorumycin和renieramycin E生成简单的异喹啉生物碱，如mimosamycin，renierone和renierol acetate。此外，从用氰化钾预处理的泰国裸鳃亚目动物Jorunna funebris中分离出了三种新的细胞毒性雷那霉素类化合物Jorunnamycins A-C，以及沿着的五种已知化合物。通过沿着化学转化，从光谱数据上确定了它们的结构。因此，雷尼霉素类药物将成为开发新型抗肿瘤药物的热点之一。

As a part of our search for new anticancer metabolites in the isolation and characterization of biologically active compounds from the Thai marine animals, we have succeeded to find blue sponges, Xestospongia sp. growing around Sichang Island in the Gulf of Thailand. We report the isolation and structure elucidation of renieramycin M as a major products pretreated marine animals with potassium cyanide in methanolic buffer solution. This is the first example for supply a gram scale of renieramycin type products from marine sources. Renieramycin M, which has potent strong cytotoxicity against several kinds of tumor cells, was easily transformed to jorumycin and renieramycin J, independently. We discovered that the oxidative degradation of jorumycin and renieramycin E to generate simple isoquinoline alkaloids, such as mimosamycin, renierone, and renierol acetate. Furthermore, jorunnamycins A-C, three novel cytotoxic renieramycin type compounds, were isolated from the Thai nudibranch, Jorunna funebris that was pretreated with potassium cyanide, along five known compounds. The structures of them ware elucidated from spectral data along with chemical transformation. Thus, renieramycins will be going up one of fascinated lead for development of new anticancer drug near future.