Natural Active Substances Arbutus Pigment And Mangiferin Structure Modification

There are three parts in this thesis:1.Structural modifications of myricetin for the improvement of its water-solublity.2.The preliminary structural modifications of mangiferin.3.Synthesis of R-methotrexate.1. Structural modifications of myricetin for the improvement of its watersolublityMyricetin, the main chemical component of bayberry bark, which is a natural flavonols compound that can inhibit platelet-activating factor-mediated platelet aggregation, thus it can be used for cardiovascular protection and cerebral ischemia. But its poor water-solublility limits the development and utilization of its injectable formulation. To increase its water-solublility, in this paper firstly myricetin sodium sulfonate was synthesized with a yield of75%and purity above98%; secondly myricetin3-glucuronide was total synthesized starting from three-hydroxyacetophenone and methyl gallate glucuronic acid with a yield of16%and purity above95%.The water solubility of myricetin sodium and myricetin3-glucuronide at room temperature is1g/500ml and1g/15ml respectively, which means that myricetin3-glucuronide’s effect is obvious.2. The preliminary structural modifications of mangiferin Mangiferin, extracted from mango leaves and Anemarrhena, is a double benzene, pyridine ketone compound, it can reduce production of uric acid by inhibiting xanthine oxidase, play the role of anti-gout activity. In order to improve its solubility and lipid-water partition coefficient, seventeen compounds were synthesized in this thesis in which7compounds were new, and the structures of all target compounds and intermediates were verified through’H NMR and mass spectrometry. The activity screening is in progress.3. Synthesis of R-methotrexateMethotrexate is one of the widely used drugs in the field of cancer chemotherapy for the treatment of various types of acute leukemia. The clinical use of methotrexate is the S-(+)-isomer while the R-(-)-methotrexate as an optical isomer impurity. The European Pharmacopoeia7.0stipulates its content shall not be greater than3.0%. But there are no standard substance in our nation, so the synthesis of R-methotrexate was studied in this paper. 0.8g R-methotrexate was synthesised, the total yield was23%with the purity>98%, and its ee%was95.1%which can be used as the standard substance in quality control of methotrexate isomer impurities.