Study On The Extraction Process Of Hypericin And The Synthesis Of Halofuginone

This paper is made up of the extraction process of Hypericin and the synthesis of Halofuginone.The first part is on the extraction process of Hypericin which contain two parts. The objective of the current study was to determine the optimum ultrasonic extraction conditions for hypericin from Hypericum perforatum L. The optimum conditions were evaluated with 2-level fractional factorial design and optimized using response surface methodology. High yields of hypericin were observed from Hypericum perforatum L. by ultrasonic extraction technology. The extraction time, acetone concentration and the ratio of solvent to material were the most significant parameters on hypericin extraction as evaluated through FFD. The extraction conditions were further investigated with central composite design. The results showed that the optimal parameters for this method were: extraction time of 36.15 min, acetone concentration of 68.14(Vol) of acetone/ethanol solvent, and ratio of solvent to material of 11.87 mL/g. Under the optimized condition, the maximum productivity of hypericin is 1.44%. The yield of hypericin under the optimized extraction conditions were great higher than that obtained from conventional solvent extraction. The present study demonstrates that ultrasonic is a great efficient tool for the fast extraction of hypericin from Hypericum perforatum L.In present study, the characteristics of eighteen macroporous resins for the static adsorption and desorption of hypericin from Hypericum perforatum L.extracts have been evaluated. And then the effect of different pH values of extract solution on the adsorption capacities of hypericin on NKA-9 resin has been explored. The Langmuir isotherm was used to describe the interactions between solutes and resins at 25℃.The results showed that a week polar resin, NKA-9, with the adsorption capacity of 12.45 mg/g (dry resin) offered the higher adsorption and desorption capacity for hypericin than other resins. The pH had a great effect on the adsorption process, and the optimum pH was 4. The adsorption process of NKA-9 at 25℃fit best to the Langmuir isotherm, proved to be single molecule adsorption.The second part is on the scale-up and optimization of process route of Halofuginone: furfuryl amine was employed as raw material though oxidation, add protective group, Williamson synthesis of ether, reduction, replacement of protective group, rearrangement, yeast chiral reduction, bromination to give the piperidine ring; 6-bromo isatin was employed as raw meterial though oxidation, chlorinated and cyclization to give 7-bromo-6-chloro-4(3H)-quinazolinone; then link the piperidine ring and quinazolinone to give the Halofuginone. The raw materials are cheap and synthetic condition is mild,so the route is suited for industrialization.