(1) Total Synthesis Of Cassiarins A And B (2) Synthesis Of Camptothecin Drug SN38 And Its New Derivatives

(1) Malaria is a very old disease which has threatened the human health for thousands years. Even in the modern developed civilization society millions of people suffered from this acute disease and died each year. In the past several centuries, many outstanding accomplishments were achieved for fighting this disease and in many parts of the world malaria has been widely eradicated. Because of the rapid spread of malaria parasites that are resistant to antimalarial drugs, the global number of cases rise again in the past dacades. So, it is extremely important to find new antimalarial drugs fighting against this obstinate disease.Cassirians A and B, two alkaloids exhibiting potent antiplasmodial activity against Plasmodium falciparum were isolated by Morita and co-workers from the leaves of Cassia siamea (Leguminosea) in 2007. From a common starting material, we developed three different total syntheses, one of which is the biomimetic synthesis. Based on these routes, three analogues of cassirian A were alos synthesized.Cancer has been becoming more and more severe to threaten human lives, and killed millions of people every year. Benefiting from the development of morden pharmaceutical chemistry and biochemistry, anticancer drugs have received more attention especially those derived from the natural sources.(2) Camptothecin, a potent anticancer alkaloid, was isolated by Wall and co-workers in 1966 from Camptotheca acuminata. Though its clinic trials was unsuccessful, Irinotecan and Topotecan, two camptothecin analogues, have been approved for treatment of several cancers. In addition, several other derivatives were also studied in different stages of clinic trials. Considering the scare natural source of camptothecin-based drugs and the future development of new derivatives, our group reported two efficient total syntheses of camptothecin and 10-hydroxycamptothecin in 2007 and 2008 respectively. Based on these achievements, we continued to accomplish the total synthesis of SN38, an active metabolite of Irinotecan, as well as the synthesis of 30 new derivatives. The biological assessment indicates that several newly developed derivatives exhibit more potent inbibitory activities against the proliferation of several cancer cells.