| Cancer is one of the fatal threats to human life and health today. The morbidity, mortality shows an increasing trend. The medication is one of the most effective means of treating cancer. With the deepening of cancer research, more and more effective anti-cancer drugs have been developed. Chemical anti-cancer drugs occupy an increasingly important role in the treatment of cancer.Camptothecin is a natural alkaloid exhibiting excellent anti-cancer activities. As a lead compound in the development of new anti-cancer drugs, camptothecin played a very crucial role. In 1996, two camptothecin derivatives, Topotecan and Irinotecan were approved for marketing by FDA. At present, there are more than ten camptothecin derivatives in various stages of clinical studies, including Gimatecan, Lurtotecan, Karenitecin, Silatecan, Diflomotecan, etc. However, the camptothecin derivatives are obtained mainly through semi-synthesis starting from natural camptothecin. Limitation of plant resources constraints the further development of camptothecin drugs to meet the growing needs of clinical trails.In 2007 and 2008, our group developed two new syntheses based on intramolecular hetero Diels-Alder reaction. Both of them have the advantages of mild conditions and high efficiency. But application of intramolecular reactions and air-sensitive organometallic reagents makes them unsatisfactory in further industrial development. Herein, we disclosed a new short and convergent route for the synthesis of camptothecin and its new derivatives. The simple operations, commercial starting materials and mild reaction conditions are advantageous for the future chemical synthesis of camptothecin family alkaloids.Furoquinolinone is the structural cores of many biologically interesting natural products and synthetic intermediates. The Hendrickson reagent-initiated cascade annulation was applied in this study to construct this kind of skeleton efficiently. |
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