Study On The Synthesis Of Berberine And Puerarin And Acute Toxicity、related Pharmacodynamic

The natural active ingredients extracted from traditional Chinese Medicine generally have a very rich pharmacological activity, it can be used as a chemical drug lead compounds corresponding structural modification. Berberine and puerarin were the effective components of traditional Chinese medicine Coptis chinensis and radix puerariae, have strong pharmacological activity. At present, the research of structure modification of themselves is more common, but it has no reports on the structure of modified between them. Therefore,it is very important to explore a way of berberine and puerarin between structural modifications of process route, seeking product with stronger or generate new pharmacological activity.With berberine hydrochloride, puerarin, raw materials, this paper is connection bridge with bromine hydride, after a few chemical reactions, stitched together with double mother nucleus structure of multicore molecules. And we conducted a preliminary study on the acute toxicity and related pharmacodynamic of the compound.The first, with berberine hydrochloride as the starting material, by the method of high temperature microwave radiation for 9 bit demethylation to obtain berberrubine. The second,9 phenolic hydroxyl of berberrubine halogenated reaction with different length of carbon chain and we get the two step product 9-0-bromic berberine hydrochloride. Finally,9-0-bromine hydride berberine hydrochloride halogenated reaction with puerarin, getting the corresponding multicore molecules. The above three steps reaction conditions were optimized screening, to obtain the optimum synthesis process. The structure of each step of the reaction products were confirmed by HPLC, UV, IR, ESI-MS,’H-NMR and 13C-NMR and other means of characterization. The obtained spliced products were studied on the toxicity experiment and some pharmacodynamics.The optimal conditions of each step are as follows. (1) demethylation reaction of berberine: ①Microwave method, microwave power 400W, microwave time 15 min, berberine/DMF ratio 1:25 (g:mL). The yields was up to 90% and the purity after purification was as high as 98%. ② Heating method:Heating to 160℃, reaction time 1h. berberine/DMF ratio 1:20(g:mL). (2) halogenated reaction ofberberrubine:30 times acetonitrile as solvent,5 times Dibromoalkane, 85℃-90℃reflux 1h, Direct cold crystallization completely, Acetonitrile, Petroleum etherwashed the filter cake. The yields was up to 90% and the purity after purificationwas as high as 96%. (3) Synthesis of multi-core molecules: Microwave method microwave power 240W,40 times DMF assolvent,7.5 times Et3N as catalyst, reaction 10 minutes; and then, the pH of thereaction mixture was adjusted to 3 by hydrochloric acid, in order to get the brown solidprecipitation. Finally, the product was Washed by water and Petroleum ether. The yields was up to 95% and the purity after purification was as highas 40%.In addition, this paper also explored the study on acute toxicity of mosaic products, the experiments show that the compounds are less toxic than berberine toxicity. After 4 weeks of drug administration, the drug did not appear hypoglycemic lipid-lowering effect. It may be the delivery period is too short, later continue to observe.Applying the principle of multi-core molecules pieced together and directingby herb couple theory, the two natural active molecules were synthesized into a multi-core molecule with two biological activity nucleus through chemical bonds of cooperation. In the way, to study its biological activity, which had a certain degree of innovation and research significance.