Study On The Biosynthesis And Biomimetic Synthesis Of Natural Products Of Tryptanthrin, Rutaecarpine Etc.

The key step of a new drug research and development is getting the bioactive compounds with acceptable price. Extraction and isolation is one important method to get the bioactive compounds, but usually expensive. If the proper synthetic method can be developed, the manufacture cost of b(?)oactive compounds will be reduced a lot. This kind of bioactive compounds will be developed to new drug possibly. In this dissertation, the biomimetic strategy was used to synthsize the tryptanthrin, rutaecarpine, 13b,14-hydrorutaecarpine, evodiamine, luotuonin A and their derivatives, in order to carry out the new drugs research and development.Tryptanthrin and its four derivatives were synthesized from isatin or its derivatives and anthranilic acid in the presence of POCl₃ in toluene and THF according to the biosynthetic route. Tryptanthrin was also synthesized by catalyzed condensation of isatin and isatoic anhydride through a convenient one- step synthesis in 80% yield .The conditions employed in the: present synthesis are mild, efficient and general. Tryptanthrin has been researched and developed as the candidate of new drug.Rutaecarpine, evodiamine and 13b,14-dihydrorutaecarpine have been synthesized by the trifluoroacetic anhydride method. A novel and practical synthetic method of rutaecarpine was designed, which was starting from acrylonitrile and diethyl malonate, via Michael addition reaction, Japp-Klingemann reaction, Fischer reaction and condensation with 56% overall yield.A novel and efficient method was applied to synthesis luotonin A, which involves the two components condensation of 3-oxo-1H-pyrrolo[3,4-6]quinoline and isatoic anhydride under alkali conditions. The important intermediate 3-oxo-1H-pyrrolo[3,4-b] quinoline was prepared by the Friedlander condensation of 2-aminobenzaldehyde and 2-oxobutyric acid, nucleophilic addition, treating with N-bromosuccinimide and ammonolysis .The total yield of four-steps synthesis of luotonin A is 52%.The distribution of tryptanthrin in Isatis indigotica Fort. was studied while the methods of treating the samples were also studied. The results suggested the tryptanthrin does not exist in the living Isatis indigotica Fort. and is a postharvest product. The postulated precursors of tryptanthrin were isatin and anthranilic acid and was supported by the precursors added biosynthesis. It was supported that the formation process of biosynthetic tryptanthrin was a chemical catalysis.