Novel Synthesis And Structural Analysis Of 5,6-dehydronorcantharidin Derivatives With 1,3-dipolar Addition Method

Cantharidin, is the major effective ingredient for the malignant tumor treatment among the people in China. Recent study proves that cantharidin can treat liver cancer to some extent, but also can enhance white cell, without inhibiting immune system. So, cantharidin is of great pharmacological interest and has gained great attention. However, cantharidin is somehow toxic and difficult to synthesize. On the other hand, the derivatives of the 5,6-dehydronorcantharidin show the same biological activity, less toxic and much easier to synthesize. Furthermore, isoxazole and pyrazole derivatives have received considerable attention over the past years due to their wide range of versatile, significant bioactivities and pharmalogical activities.As many compounds containing 1,2,3-trizolyl have become a hot topic in heterocyclic compounds because of their antitumor, anti-virus, analgesic, sedative and fungicidal activities. It has been shown recently the pharmacological activities of parent molecules will apparently be improved with the introduction of 1,2,3-triazolyl to some active molecules, such as Penicillin, Cephalesporins and so on. Tests with derivatives of quinoxaline show them have anticancer, anti-HIV, antifungal, antidepressant, anthelmintic and herbicidal properties. Although 1,3-dipolar cycloaddition reactions of nitrile oxide is the general method to synthesize isoxazoline, there has been very little work on the 1,3-dipolar cycloaddition reaction of 5,6-dehydronorcantharidin derivatives. These observations prompted us to study the synthesis of 5,6-dehydronorcantharidin derivatives, we successfully design and efficiently synthesize the 5,6-dehydronorcantharidin isoxazoline adducts. These kinds of compounds have wide applicative prospect. Therefore, we expect to realize reinforcement of physiological activities by means of combining isoxazolewith different heterocycles of norcantharidin derivative. It extended the research field of such compounds and provided abundant leading compounds for later selecting work of effective drugs.This thesis consists of two major parts:The first part is about literature review. The progress in application and synthesis of cantharidin and norcantharidin; the development in the synthesis of norcantharidin derivatives; the theory of Diels-Alder and 1,3-dipolar addition.The second part is about experimental content. Major work as follows:1, By means of Diels-Alder addition, we successfully synthesized the norcantharidin and its derivatives; Synthesis of novel antitumor chemotherapeutic agents: 5,6-dehydronorcantharidin and isoxazoline derivatives;2, Synthesis of novel antitumor chemotherapeutic agents: 5,6-dehydronorcantharidin and pyrazoline derivatives;3, Synthesis of novel antitumor chemotherapeutic agents: 5,6-dehydronorcantharidin derivatives containing 2-phenyl-l,2,3-triazolyl.