合成具抗氧化活性的氨黃酮醇化合物及利用奎寧酸合成含氟多醇六環類醣分子

Syntheses of Aminoflavonols as Antioxidants and Fluorocyclitols from D-(-)-Quinic Acid

廖文瑜(Wen-Yu Liao)

指導教授 ： 施增廉

淡江大學/理學院/化學學系碩士班/碩士(2014年)

https://doi.org/10.6846/TKU.2014.01204

摘要

黃酮醇類化合物廣泛地存在於自然界中，它們具有良好的抗氧化效果，因此多利用為生物體內的自由基清除劑、氧化酶抑制劑及抗癌藥物等等。
天然或合成的氨黃酮類非常稀少，且從自然界中直接提煉黃酮醇效益不高，因此本論文以黃酮醇為主要結構並以合成方式製備氨黃酮醇化合物。有別以往的合成方式，我們使用具有鹵素的芳香族為起始物，首先進行羥醛縮合反應 (aldol condensation) 得到查爾酮分子 (chalcones)，經由阿爾格-弗林-大山田氧化反應 (Algar-Flynn-Oyamada oxidation) 獲得含溴的黃酮醇化合物，再以 TMSN3、使用銅催化的新方法將溴直接轉換成氨基，如此便可利用高效率方式獲得氨黃酮醇的目標化合物。
本論文另一部分為立體選擇性合成含氟六環多醇分子。六環多醇分子 (Cyclitols) 為一類醣分子，其生物活性一直以來都受到極大的關注，目前已知特定的衍生物可作為抗生素、有抑制腫瘤及糖尿病等功能。而在此分子中引入氟原子的目的，是因氟具有改變分子通透性、增加化學穩定性等優點，希望能更加提升生物活性。
我們利用D-(-)-quinic acid 為起始物，將其中部分氫氧基適當的保護後，將特定的氫氧基以DAST氟化，再利用OsO4 / NMO 系統進行羥基化反應 (dihydroxylation) ，根據反應不同的立體選擇性合成出多種不同位向的含氟多醇六環類醣分子 (fluorocyclitols)。

關鍵字

阿爾格-弗林-大山田氧化反應 ； 氨黃酮化合物 ； 含氟多醇六環類醣分子 ； 立體選擇性

並列摘要

Flavonols are naturally occurring molecules. They are recognized as good antioxidants. Many flavonols are used for reactive oxygen species scavengers, oxidase inhibitors and anticancer drugs.
Aminoflavonols are relatively rare to be found in nature, and their purification from natural products is not practical. Therefore we employed flavonols as the main framework to synthesize aminoflavonols. We utilize bromoaromatic compound as starting material. The key steps were employed aldol condensation, followed by Algar-Flynn-Oyamada oxidation (AFO oxidation) to synthesize bromoflavonols. Subsequently, the bromine group was replaced with amino group by TMSN3 and catalyzed by copper powder to obtain aminoflavonols in a facile manner.
The second part, was stereoselective synthesis of fluorocyclitols. Cyclitols are cyclohexanes containing three or more hydroxyl groups. Its bioactivity is attracted much attention by scientists. Some specific derivatives of cyclitols are used as antibiotics, anticancer drugs and antidiabetes.
The replacement of hydrogen atom(s) of cyclitols with fluorine atom(s) is considered to improves molecular permeability, chemical stability, promote bioactivities. We use D-(-)-quinic acid as starting material, partial of hydroxyl groups were appropriate protected. One of hydroxyl group is fluorinated by DAST, followed by OsO4/NMO for dihydroxylation. Based on the stereoselectivity of the reaction, fluorocyclitols with various stereochemistry were obtained.

並列關鍵字

Algar-Flynn-Oyamada oxidation ； Aminoflavonol ； Fluorocyclitol ； Stereoselective

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