Research On The Synthesis Of Puerarin Derivatives And The Converted Pyrazole Compounds

Puerarin is a natural occurring isoflavone extracting from puerarin lobata or puerarin thomsonii, which is mainly used for the treatment of cardio-cerebrovascular diseases in clinical medicine, such as angina, coronary heart disease, myocardial infarction, etc. The water-soluble, oil-soluble and bioavailability of puerarin are relatively low owing to its structure of isoflavone. Puerarin derivatives can be obtained by modifying the structure of puerarin, which not only can keep the original treatment effect, but also improve its solubility. The pyrazole compounds can be obtained using the reaction of hydrazine hydrate and puerarin derivatives. The 3,4-diarylpyrazole compounds have good biological activity, which show the effect such as good antitumor, bacteriostat and weight loss. At the same time, these compounds have the advantages of high efficiency, low toxicity and can be used as the lead compound in the process of drug development. As glycosyl is a structure that has more hydroxyl which easy to form hydrogen bonds, make the target molecules combine with target more effectively, change its solubility and guidance, and enhance the receptor affinity ability. Due to the instroduction of glycosyl, the biological activity and physiological function of 3,4-diarylpyrazole compounds were enchanced.In this paper, puerarin derivatives and pyrazole compounds were synthesized.15 puerarin derivatives were synthesized by the alkylation reaction of phenolic hydroxyl group and electrophilic substitutive reaction of aromatic ring, using puerarin as raw material.11 of them increase solubility in organin solvent,4 in the water solubility increase. Among these puerarin derivatives, 7-butoxypuerarin,7,4'-dibutoxypuerarin and 3'-isopropylpuerarin were not been reported. Meanwhile,3',5'-dihydroxy methyl puerarin has been reported for the first time. The optimum synthetic conditions of 3',5'-dihydroxy methyl puerarin were studied by the four factors and three levels orthogonal experiment. The molar ratio is purearin:methanol:sodium hydroxide= 1:2:4, the reaction temperature 60? and the reaction time 4h. The structure of synthetic compounds was characterized by IR,1H NMR,13C NMR spectra and elemental analysis. The solubility experiments of puerarin derivatives have been tested, solubility in organic solvent or water has been increased.Thirteen novel 3,4-diarylpyrazole containing a glucosyl group were synthesized by hydrazine hydrate, puerarin and its derivatives, with hydrazine hydrate in intermolecular cyclization reaction [3+2]. This novel synthetic method Provides several advantage such as shortened process, simple workup procedure and high yield. The structures of these compounds were characterized by IR, 1H NMR,13C NMR spectra and elemental analysis, and all compounds were not been reported. This thesis analyzes eaction mechanism, and discusses the the influence of solvent, reaction temperature and alkali dosage on the yield. And the optimum reaction condition is that the reaction temperature is 85?, the best solvent is absolute ethanol and the hydrazine is more, because hydrazine is both alkaline and nucleophile. The solubility of products in water were tested, which solubility is good and basically meet the needs of clinical application. We have carried on the in vitro antibacterial activity test to products. Because the choosing gram negative bacteria and gram-positive bacteria can both strongly inhibit the bacteria, and the MIC of some products is closely to positive control bacterias, the products are expected to become a new bacteriostatic drugs.