黄芩素全合成及其酰化Mannich碱衍生物结构设计-药物化学专业毕业论文.docxVIP

黄芩素全合成及其酰化Mannich碱衍生物结构设计Total 黄芩素全合成及其酰化Mannich碱衍生物结构设计 Total Synthetic of Baicalein and Structure Design of Acylation Baicalein Mannich Base Derivatives Abstract Cyclin—dependent kinase fCDK)l is the only necessary in the process of cell proliferation and has become the latest target for anti—cancer drugs．Natural flavonoids are some CDK 1 selective inhibitors，and activity of Baicalein is strongest．Baicalein does not directly kill cells，but selectively induced apoptosis in tumor cells through different mechanisms of redox state normal cells and tumor cells and regulation of intracellular reactive oxygen species，without affecting normal cell function．However，its poor solubility and low bioavailability limited its clinical application．Therefore，structure modification of Baicalein used as leading compounds aroused people’S concern． In this paper，Phloroglucinol dihydrate and Acetonitrile as material，Phosphorus oxychlofide as catalyst，Trihydroxy benzene ethylene imine was synthesized by Hoesch reaction，and then Trihydroxy acetophenone monohydrate was synthesized by hydrolysis (yield 85．5％，purity 98．O％)．6一Acetyl-Chrysin was synthesized by depressor reaction，using Trihydroxy acetophenone monohydrate and Benzoyl acetic acid ethyl ester as the raw material(yield 65．O％，purity 95．O％)．6-Acetyl Chrysin as material，after 4％NaOH dissolution，oxidation of H202 and acidification of acetic acid，Baicaleinwas totally synthesized(yield 86．6％，purity 96．0％)．Three new compounds：6一Acetyl—Baicalein，6。 Benzoyl．Baicalein and 6-Butyryl—Baicalein were synthesized by acylation，using Baicalein as material． Baicalein，6-Acetyl-Chrysin and acylation of Baicalein used as lead compounds，6 Flavone Mannich base derivatives were semi-synthesized by Mannich condensation reaction with organic amines and formaldehyde in organic solvents：8一Hydroxypiperidine—methyl- Baicalein(BA-j)，6一Acetyl-8一Hydroxypiperidine-methyl—Chrysin(CH-j)，6一Acetyl-8。 Hydroxypiperidine—methyl—Baicalein(ACBA-j)，6-Acetyl-8-Hydro