四硼Ugi化合物之合成及其作為BNCT藥物之生物測試

The Synthesis of Tetra Boron-containing Ugi Analogous and their Biological Evaluation as the Potential BNCT Agent

邱碩蓓(Shuo-Bei Qiu)

指導教授 ： 潘伯申

淡江大學/理學院/化學學系碩士班/碩士(2018年)

https://doi.org/10.6846/TKU.2018.00349

摘要

利用Ugi Reaction合成四硼化合物(I)
本研究將對含硼異腈與其他含硼化合物之Ugi-4CR反應進行優化，並成功地以微波反應合成出9個含4個硼酯官能基之含硼雙胜肽化合物。這一系列的化合物，在單位分子含硼量較高，我們預期它在BNCT療程中會有所表現。
硼酯官能基之去保護(II)
本研究嘗試了三種將硼酯官能基去保護成硼酸化合物，將對這些方法進行討論，由於含硼化合物的純化不容易，希望能找出效率高、產率高的方法，提升含硼化合物的產量。
四硼化合物之生物測試(III)
我們將對本實驗室合成的含硼化合物、含硼果糖化合物、BNCT臨床用藥BPA做比較，藉由硼酸化合物會與DAHMI結合，在U2OS細胞的螢光圖中會發亮，可以得知含硼化合物聚集於細胞核，且透過螢光圖來看會比BPA來的亮，進一步利用流氏細胞儀來判斷這些進入細胞的含硼藥物進入細胞所發出的螢光量，並對這些研究做討論。

關鍵字

硼中子捕獲治療 ； 多組成反應 ； 生物測試

並列摘要

1. Synthesis of Tetra Boron-containing Ugi Analogous :
In this study, the Ugi-4CR reaction of boron-containing isocyanide with other boron-containing compounds was optimized, and nine boron-containing double peptiods containing four boronate esters functional groups were successfully synthesized by microwave reaction. These compounds could be potentially utilized in boron neutron capture therapy due to their high boron content.
2. Boronate Esters Functional Groups Deprotection :
In this study, we attempt three way to deprotect boronate esters functional groups into boronic acid compounds will be discussed. Since the purification of boron-containing compounds is not easy, it is hoped that high-efficiency, high-yield methods can be identified and boron-containing compounds can be improved yield.
3. Biological Evaluation of Tetra Boron Analogs :
We will compare boron-containing compounds, boron-containing fructose compounds synthesized in our laboratory, and BNCT clinically used BPA. By binding boronic acid compounds to DAHMI, they will glow in the fluorescence of U2OS cells. Gathered in the nucleus, and brighter than the BPA through the fluorescence chart, and further use of the rheometer to determine the amount of fluorescence of these boron-containing drugs entering the cells to enter the cell, and discuss these studies.

並列關鍵字

BNCT ； Boron ； Multicomponent ； Biological Evaluation

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