The Synthesis And Research Of Bis(Indolyl)Methanes And Novel Isoxazole Derivatives

The bisindole methane compounds and their derivatives is a very important class of heterocyclic compounds with high biological and pharmacological activities. It can adjust some of the carcinogenic metabolites, which can prevent cancer. For example, for breast cancer prevention. It also has anti-fungal and anti-tumor effect. Thus it has a very important value in the field of drug research and development. Oxidation of bisindole methane compounds containing conjugated bisindole-based skeleton is also used as a colorimetric sensor. Therefore, the synthesis of bisindole methane compounds has a great value.There are many ways to synthesize the bisindole methane compounds, generally using a protonic acid or Lewis acid catalysis. But it requires adding an excess of acid, the reaction conditions are more stringent, and the post-processing causes environmental pollution. Lewis acid general requirements for anhydrous, and will captured by nitrogen-containing substrates, thus it need to be added more than the stoichiometric. Lithium perchlorate can solve these problems, but it is more expensive, relatively long reaction time. A catalyst containing rare earth metals or ionic liquids are expensive. But the reaction time is longer, the yield is not high.Microwave has been used for chemical synthesis of large numbers of compounds, it can significantly reduce the reaction time with less byproduct, the reaction is very clean. The solvent-free reaction is a technology to avoid harmful solvents in organic reactions. It can shorten the reaction time, the yield is high and it may increase the stereoselectivity of the reaction, and the post-processing is very simple.In our work, we use the solvent-free conditions, silica catalysis, microwave synthesis method. The first10kinds of aromatic aldehydes with indole reaction,85%-98%yield to get aromatic substituted bisindole methane compounds. The yield of the reaction is high and the reaction time is very short, only10minutes. Isoxazole derivatives is very important pharmacologically active pharmacophore.It is often used as useful intermediates for the synthesis of natural products of biological activity. As the further study of the method, we use aldehyde containing isoxazole ring and indole reaction with the same method,94%-99%yield to get the bisindole methane compounds containing isoxazole ring. Isoxazole derivatives with good biological and pharmacological activity, the activity of the bisindole methane compounds containing Isoxazole ring might be better. At the same time, the reaction yield is high, and also proved that the method has universal applicability.1,3-dipolar cycloaddition is the best way to build the isoxazole ring. Our method is double use of1,3-dipolar cycloaddition to synthesize18kinds of new isoxazole derivatives containing isoxazole ring. The second use of1,3-dipolar cycloaddition reaction in our strategy, we use anhydrous zinc chloride as a catalyst, byproduct rarely and yield moderate to good. Center structure of the heterocyclic skeleton are generally drug or class of drug molecules, the isoxazole ring itself is a good active pharmacophore The new isoxazole derivatives synthesized in this paper, containing two isoxazole ring, the heterocyclic skeleton may have very good biological and pharmacological activity. Follow-up can test the biological activity of these compounds, as well as the introduction of the pharmacophore, such as pyridine to the heterocyclic skeleton to synthesize more new isoxazole derivatives with better biological activity.In summary, our work are in the microwave solvent-free conditions, silica catalytic synthesis of16different bisindole methane compounds. And using1,3-dipolar cycloaddition to construct the heterocyclic skeleton containing two isoxazole ring, and synthesized18kinds of new isoxazole derivatives.