Medicinal chemistry on marine alkaloid as a seed of the development for a new anticancer drug in Malaya area

Ecteinascidin 743是从海洋被囊动物Ecteinascida turbinata中分离得到的一种天然产物，目前已在美国和欧盟进行了II/III期临床试验。作为我们寻找新的抗癌代谢物的分离和表征的生物活性化合物从泰国海洋动物的一部分，我们已经成功地找到了泰国被囊动物，Ecteinascida thurstoni Herdman 1891，这是第一个例子的亚洲被囊动物含有这类分子，生长在普吉岛周围。我们报告的分离和结构鉴定ecietnascidins 770和786从KCN预处理的泰国被囊动物。使用该方法分离天然海产品具有增加不稳定的海鞘素型化合物的产率的优点。此外，我们还发现了一种蓝色海绵，Xestospongia sp.，生长在泰国湾的四昌岛附近，通过同样的策略，我们成功地分离出克级的renieramycins M，它也具有强有力的抗肿瘤活性。顺便说一下，最有趣的问题之一，即如何保持用于药物开发的海鞘素的稳定供应：通过从海洋来源分离还是通过全合成仍然存在。在开发这一系列天然产物的短步骤合成方面，我们以前曾报道过三环内酰胺中间体的制备和ABC环模型化合物的部分合成。鼓励我们的研究结果，我们应用这些策略的ABCDE环系统的ecteinascidins，在两个苯环上具有特征取代基的准备。

Ecteinascidin 743 is a natural product isolated from the marine tunicate Ecteinascida turbinata, which has been demonstrated to be a highly promising, exceeding potent antitumor agent currently in phase II/III clinical trials in USA and EU. As a part of our search for new anticancer metabolites in the isolation and characterization of biologically active compounds from Thai marine animals, we have succeeded to find a Thai tunicate, Ecteinascida thurstoni Herdman 1891, which is the first example of the Asian tunicate containing this class of molecules, growing around Phuket Island. We report the isolation and structural elucidation of ecietnascidins 770 and 786 from the KCN pretreated Thai tunicate. Isolation of natural marine products using this procedure has the advantage of increasing the yield of labile Ecteinascidin-type compounds. Furthermore, we found a blue sponge, Xestospongia sp., growing around Sichang Island in the Gulf of Thailand, and by the same strategy, we are succeeded the gram-scale isolation of renieramycins M, which has also potent amtitumor activity.By the way, one of the most intriguing problems, which is how to maintain a consistent supply of ecteinascidins for drug development : by isolation from marine sources or by total synthesis still remains. In connection with the development of a short-step synthesis of this series of natural product, we have previous reported the preparation of the tricyclic lactam intermediate, and the partial synthesis of the ABC ring model compound. Encourage by the results of our studies, we apply these strategies for preparation of the ABCDE ring system of ecteinascidins, having characteristic substituents in both benzene rings.