The Synthesis And Properties Of Scutellarein-appended β-cyclodextrin Andβ-Cyclodextrin-grafted N-succinylε-Poly-L-Lysine

Drug cyclodextrin conjugate has been one of the significant topics in supramolecular chemistry. With regards to its structure, cyclodextrin could be as a durg carrier to targetedly control drug release.In order to study the synthesis process of cyclodextrin conjugate, we choose scutellarein with anticancer activity as bioactive molecule onto cyclodextrin in this thesis. We have confirmed the structure of the conjugate, and also researched the character of the conjugate. The antiproliferative activity of the conjugate has been evaluated in vitro by the MTT cytotoxicity assay.ε-Poly-L-Lysine and cyclodextrin are both considered as a drug control-released carrier or targeted drug delivery carrier. Therefore, how to immobilize cyclodextrin onto ε-Poly-L-Lysine has important practical significance in combining their advantages and being used for the field of drug controlled release. In this thesis, a type of CD-grafted N-succinyl ε-Poly-L-Lysine composed of e-Poly-L-Lysine and cyclodextrin derivatives was synthetized. Meanwhile,β-CD-grafted N-succinyl ε-Poly-L-Lysine/drug molecular inclusion system was prepared. The cyclodextrin inclusion complex will improve the targeted drug release and increase the drug loading. The major contents of this thesis are as follows:1. Used the concentrated acid-splitting and dilute acid-splitting, scutellarein was successfully prepared from scutellarin. The ilute acid-splitting process was optimized with orthogonal experiment to obtain the optimal prepared condition for scutellarein from scutellarin. And its structure was charactered by UV and1H-NMR spectroscopy.2. Respectively used Mannich reaction and Blanc reaction, a new scutellarein-appended β-cyclodextrin was prepared, and its structure was determined by1H-NMR spectroscopy and MS. Both its water solubility and cytotoxicity were evaluated.3. The two ε-Poly-L-Lysine derivatives were synthesized from cyclic anhydride and ε-Poly-L-Lysine, namely N-succinyl ε-Poly-L-Lysine and N-maleoyl ε-Poly-L-Lysine. The structures of this two ε-Poly-L-Lysine derivatives were confirmed by’H-NMR spectroscopy.4. The three β-CD-grafted N-succinyl ε-Poly-L-Lysine were synthesized from N-succinyl ε-Poly-L-Lysine and6-en-β-CD,6-dien-β-CD and6-trien-β-CD. The structures of the products were determined by1H-NMR spectroscopy.5. The inclusion complexes ofβ-CD-grafted N-succinyl ε-Poly-L-Lysine with dihydroartemisinin (DHA), artemether(ATM) and scutellarein(SCUE) were prepared. The structures of the inclusion complexes were approximately determined by1H-NMR spectroscopy.