- 學位論文
多甲基咖啡酸二聚體及三聚體作為抗愛滋病毒試劑之不對稱全合成與迷迭香酸之全合成
Asymmetric Syntheses of Polymethylated Caffeic Acid Dimers and Trimers as Anti-HIV Agents and Total Synthesis of Rosmarinic Acid
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摘要
於本篇論文中，本人成功發展一個不對稱合成路徑以合成a-羥基甲基酯以及其鏡像異構物，應用此不對稱合成子可合成多甲基迷迭香酸及丹酚酸甲、丙和丁。此外，本人亦報導經由五步驟反應，總產率為28%之七甲基紫草酸新型合成路徑，利用鎂金屬於甲醇溶液中進行立體選擇性還原苯并呋喃，建構具有對位位向之二氫苯并呋喃核心結構之七甲基紫草酸。 此類型化合物抗愛滋病毒複製之生物活性亦在本篇探討。其中，多甲基(+)-迷迭香酸以及(±)-丹酚酸丙具有抑制HIV-1RTMF (AZT-resistant)病毒複製之生物活性，其IC50 分別為34 uM 及50 uM。最後，本人用異丁基二甲基矽烷基做為理想之保護基以完成多酚酸之全合成。迷迭香酸之全合成以咖啡酸為起始物可於七個步驟完成，其總產率為42%。並且，此高效率路徑可用以合成oresbiusin B、丹酚酸丙、及丁之骨架。
並列摘要
In this thesis, asymmetric syntheses of methyl lactate and its antipode has been discussed. Application of these chiral synthons culminated in the asymmetric syntheses of both the antipodes of polymethylated rosmarinic acid, salvianolic acid A, salvianolic acid C, and salvianolic acid D. In addition, a modular, flexible, and convergent route to the heptamethyl lithospermic acid has been described. The heptamethyl lithospermic acid was accomplished in 5 steps from the known compounds in 28% overall yield. The trans-dihydrobenzofuran core of heptamethyl lithospermic acid was achieved by stereoselective reduction of benzo[b]furan with magnesium in methanol. Furthermore, an alternative method for the synthesis of trans-cinnamic acid derivative has been devised and can be applicable for enantioselective synthesis of lithospermic acid. The biological activity of polymethylated caffeic acids against HIV-1 virus replication was evaluated. Among them, polymethylated (+)-rosmarinic acid and (±)-salvianolic acid C were found to inhibit the replication of HIV-1RTMF (AZT-resistant) virus with IC50 values of 34 µM and 50 µM respectively. Also, this thesis presents the total synthesis of polyphenolic acids which exploits tert-butyldimethylsilyl (SiMe2t-Bu) as an ideal protecting group. In order to prove that, total synthesis of (±)-rosmarinic acid was completed in 7 steps and 42% overall yield from caffeic acid. Furthermore, efficient and flexible routes were established for the syntheses of orthogonally protected skeleton of oresbiusin, salvianolic acid C, and salvianolic acid D.
並列關鍵字
無資料參考文獻
(15) Wagner, H.; Wttmann, D.; Schaefer, W. Tetrahedron Lett. 1975, 8, 547550.
(58) Lee, G. H.; Youn, I. K.; Choi, E. B.; Lee, H. K.; Yon, G. H.; Yang, H. C.; Pak, C. S. Curr. Org. Chem. 2004, 8, 12631287.
(60) Yuen, M. S. M.; Xue, F.; Mak, T. C. W.; Wong, H. N. C. Tetrahedron 1998, 54, 1242912444.
(63) Nakanishi, T.; Suzuki, M.; Mashiba, A.; Ishikawa, K.; Yokotsuka, T. J. Org. Chem. 1998, 63, 4235–4239.
(31) Chen, H.; Teng, L.; Li, J. N.; Park, R.; Mold, D. E.; Gnabre, J.; Hwu, J. R.; Tseng, W. N.; Huang, R. C. J. Med. Chem. 1998, 41, 30013007.
延伸閱讀
- 曾秉曜（2019）。一、透過鹼控制高醯基香豆素與 1,3-茚二酮衍生物進行化學選擇性 1,6-Addition/Aldol 或 1,6-Addition/Michael 連續反應合成香豆素衍生物二、透過有機膦試劑、酸酐與亞芳基-1,3-茚二酮合成茚並[1,2-c]呋喃衍生物〔碩士論文，國立臺灣師範大學〕。華藝線上圖書館。https://doi.org/10.6345/NTNU201900071
- Chung, C. L. (2009). 新型含三氟甲基取代之萘環結構的芳香族二醚二胺所衍生之有機可溶性及低介電常數之聚醯亞胺之合成與性質 [doctoral dissertation, Tatung University]. Airiti Library. https://www.airitilibrary.com/Article/Detail?DocID=U0081-3001201315104817
- Lee, A. R., Sung, K. S., & Huang, W. H. (1993). 高壓液相層析法定量口服鎮痛錠劑成分咖啡（生僉）、乙氧基苄醯胺及異丙安替比林. 藥物食品分析, 1(4), 351-356. https://www.airitilibrary.com/Article/Detail?DocID=10219498-199312-1-4-351-356-a
- Hébert, M. J. G., Flewelling, A. J., Clark, T. N., Levesque, N. A., François, J. J., Surette, M. E., Gray, C. A., Vogels, C. M., Touaibia, M., & Westcott, S. A. (2015). Synthesis and Biological Activity of Arylspiroborate Salts Derived from Caffeic Acid Phenethyl Ester. International Journal of Medicinal Chemistry, 2015(), 24-32. https://doi.org/10.1155/2015/418362
- 熊子瑢（2008）。SYNTHESIS AND ELECTROCHROMISM OF POLYAMIDES AND POLYIMIDES WITH 2,4-DIMETHOXYLTRIPHENYLAMINE MOIETY〔碩士論文，大同大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0081-0607200917245209