臺灣博碩士論文加值系統

Antrocamphin A為牛樟芝(Antrodia cinnamomea)組成分中之活性化合物，具有抑制經fMLP誘導而產生超氧陰離子(superoxide anion)之抗發炎活性。本研究將著重於antrocamphin A與其衍生物之SARs之探討，及antrocamphin A之全合成設計與生物活性之評估；此全合成設計是以o-vanillin為起始物的六個步驟之合成路徑。
實驗結果共合成antrocamphin A之全合成及17個衍生物，而抗發炎活性試驗中，化合物CH-15、CH-16、CH-17與CH-F1表現具有抑制因LPS誘導巨噬細胞產生的NO自由基，在濃度20 μg/mL下，抑制率分別為97％、77％、84％ 與 98.1％。而在抗血小板凝集試驗中，化合物CH-02對於collagen引起的血小板凝集具有最佳之抑制能力，其IC50值為1.16 μg/mL。

Antrocamphin A is an active natural product from Antrodia cinnamomea (Taiwanofungus camphoratus), which exhibited potency of anti-inflammatory effect by suppressing fMLP-induced production of superoxide anion. To explore the SARs of antrocamphin A and its derivatives, the total synthesis of target analogues were designed and achieved for biological activity evaluation. The natural product, antrocamphin A, was total synthesized in six steps, started from o-vanillin.
Finally, the antrocamphin A(CH-F1) and seventeen derivatives (CH-01~CH-05, CH-07~CH-18) were synthesized. Based on the results of anti-inflammatory activity assay, derivatives with enyne substitution CH-15~CH-17 and antrocamphin A exhibited potent inhibition against NO production in LPS-induced macrophages with 97％, 77％, 84％ and 98.1％ at the concentration of 20 μg/mL, respectively.In the anti-platelet aggregation activity assay, compound CH-02 showed significantly potent anti-platelet aggregation induced by collagen with the IC50 value of 1.16 μg/mL.

目錄 ........................................................................................................... I
圖表目錄.................................................................................................II
Abstract ..................................................................................................V
中文摘要............................................................................................... VI
第一章 緒論.............................................................................................1
第一節 前言......................................................................................1
第二節 文獻回顧..............................................................................3
第三節研究目的............................................................................27
第四節逆合成分析........................................................................28
第二章 合成機制探討與實驗方法................................................32
第一節Antrocamphin A之全合成方法-scheme 1 .............32
第二節Antrocamphin A之全合成方法-scheme 2 .............34
第三節Antrocamphin A之全合成方法-scheme 3 .............36
第四節衍生物之合成方法.......................................................38
第五節Antrocamphin A合成機制之推論-Scheme 3...................39
第六節 實驗材料...........................................................................43
第七節 化學合成之實驗方法........................................................45
7.1 Antrocamphin A之全合成 ..................................... 45
7.2 衍生物之合成 ......................................................... 51
第八節 儀器與材料........................................................................67
第九節 生物活性試驗之實驗方法................................................69
第三章 結果與討論...............................................................................72
第一節 抑制LPS誘導小鼠巨噬細胞產生NO自由基之活性...72
第二節 抑制血小板凝集活性........................................................77
第四章結論...........................................................................................79
第五章 化合物之光譜數據.............................................................80
第六章參考文獻..............................................................................118

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