Synthesis And Study Of New Compounds Tetrahydroxy Protoberberine

Alkaloids are compounds with similar isoquinoline structure and included coptis ine, berberine, jateorhizine, palmatine and epiberberine. Tetrahydropalmatine and2,3,9,10-tetra-n-butoxyprotoberberine was synthesized from Coptids Rhizoma by reaction s:demethylene-dioxy or demethylation, hydrogenation, methylation and butylation, o xidation, and the yield of tetrahydropalmatine and2,3,9,10-tetra-n-butoxyprotoberberi ne were18%and16%. The structures were confirmed by UV, IR,1H-NMR and E SI-MS. Through the single-factor experimental design, the synthesis conditions of2,3,9,10-tetra-n-butoxyprotoberberine and tetrahydropalmatine were studied to get the b est process conditions. Cryptococcus, Candida krusei, Staphylococcus aureus, and Ca ndida albicans were for the experimental bacterium. The value of MIC is tested.The best synthesis conditions for the experiment on the premise of the comprehe nsive consideration factors such as raw materials, cost, time and efficiency are as f ollows:alkaloids first were demethoxy and demethylenedioxy and then hydrogenated to obtain tetrahydropalmatine and2,3,9,10-tetra-n-butoxyprotoberberine after methyla tion and butylation, oxidation. The condition for synthesis of tetrahydro alkaloids of Coptis chinensis:molar ratio of BBr3to tetrahydro alkaloids is8:1and reaction ti me is16h. The condition for synthesis of tetrahydrotetrahydroxy alkaloids of Copti s chinensis:return temperature80℃; molar ratio of KBH4to raw material5:1; mol ar ratio of catalyst K2CO3to raw material9:1and reaction time6h. The condition for synthesis of tetrahydropalmatine:molar ratio of Me2SO4to raw material5:1:m olar ratio of NaOH to raw material5:1and reaction time5h. The condition for sy nthesis of123:molar ratio of n-BuI to raw material5:1:molar ratio of catalyst K2CO3to raw material5:1:reaction temperature80℃and reaction time8h. The con dition for synthesis of2,3,9,10-tetra-n-butoxyprotoberberine:molar ratio of catalyst CH3COONa to raw material4:1, molar ratio of I to raw material3:1and reaction t ime12h.The results showed that:tetrahydropalmatine and2,3,9,10-tetra-n-butoxyprotober berine had maintained and even increased the antibacterial properties of berberine a nd berberrubine and the value of MIC is16μg/mL and8μg/mL. The mechanism of their antibacterial may due to that the prepared product has higher lipophilic and enhance the permeability of the drug on the cell membrane.