臺灣博碩士論文加值系統

近年來，許多關於設計及合成醣解酵素抑制劑（glycosidase inhibitors）被廣泛報導，並引起學術界和工業界的濃厚興趣。因為這些抑制劑被認為適用於癌症、病毒感染、糖尿病、內分泌失調等症狀，且具有潛力可發展成為新藥物。 Polyhydroxylated piperidines的衍生物，和醣分解酵素之間擁有奇特和有趣的作用，所以有潛力發展成為醣分解酵素抑制劑。它們擁有和一般的醣類相似的結構，不同的是由一氮原子取代環上面的氧原子，所以又被稱為azasugars或是iminosugars。例如，1,4,5-trideoxy-1,5-imino-D-lyxohexitol，即為一種azasugars，據文獻報導它可經由3-deoxy-D-hexose合成，其對於α-D-glucosidase、β-D-glucosidase與β-D-galactosidase都表現出具有潛力的抑制效果。所以我們參考此分子，利用D-(-)-quinic acid為起始物，經過11個步驟成功合成一新的trihydroxy piperidine － (2S,4R,5S)-2- hydroxymethyl-piperidine-4,5-diol。另外，文獻曾經報導過，quercitols的相關衍生物sylvestre，也是一種醣分解酵素抑制劑。而quercitols家族擁有共16種的立體異構物，其中4種是具有內對稱面的化合物，分別是neo-、cis-、scyllo- 與muco-quercitols。其他12種被分為6對的光學鏡像物。由合成上述的iminosugar過程中發現，我們可以利用D-(-)-quinic acid經過一些簡易的轉換，得到(1R,4R,5R)-triacetoxy-cyclohex-2-ene分子。然後再經過dihydroxylation，就可以得到(+)-proto-quercitol。同時我們合成了一系列具立體化學特異性的(1,4,5)-triacetoxy-cyclohex-2-ene，相信在未來可合成各式各樣的quercitols。

Recently, the syntheses of glycosidase inhibitors have attracted a great deal of attention in academies and industries. These glycosidase inhibitors possess potential in the treatment of cancers, HIV, diabetes and metabolic disorders.The polyhydroxylated piperidines (called “azasugars” or “iminosugars”) have been known as glycosidase inhibitors. They display the same stereochemical information as common hexoses, but a nitrogen atom replaced the ring oxygen of the corresponding pyranose. Among these azasugars, the representative morecu1es, such as 1-deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (DMJ), are strong inhibitors of glucosidase and mannosidase, respectively. Furthermore, 1,4,5-trideoxy-1,5-imino- D-lyxohexitol was synthesized from 3-deoxy- D-hexose and showed good inhibitory activity against theα-D-glucosidase, β-D- glucosidase andβ-D-galactosidase. Our ongoing project is aiming at the synthesis of various glycosidase inhibitors. Thus we reported a new 2,3-epi trihydroxy piperidine, (2S,4R,5S)-2-hydroxymethyl-piperidine-4,5- diol, which was synthesized in eleven steps starting from D-(-)-quinic acid.In addition, the family of quercitols possessed 16 stereoisomers. Among these isomers, (+)-proto-quercitol was isolated first in 1849 but its synthesis was not complete until 1968 by McCasland. We employed (1R,4R,5R)-triacetoxy-cyclohex-2-ene which was derived from the proper transformation of D-(-)-quinic acid to synthesize (+)-proto-quercitol. With the accomplishment from the above, we synthesize a series of protected chiral (1,4,5)-cyclohex-2-ene triols, which can be used in the syntheses of a variety of quercitols in the future

目錄
中文摘要………………………………………………………………..Ⅰ
英文摘要………………………………………………………………..Ⅱ
目錄……………………………………………………………………..Ⅲ
圖表目錄………………………………………………………………..Ⅳ
附圖……………………………………………………………………..Ⅵ
縮寫名詞……………………………………………………………......Ⅸ
第壹章 前言……………………...…………………………………...…1
1-1. 醣分解酵素與醣分解酵素抑制劑…………………………………1
1-2. 研究動機……………………………………………………………2
第貳章 結果與討論………………………………………….……….....9
2-1. Trihydroxyl piperidines的合成部分……………………….………..9
2-2. 1,4,5-Triacetoxy-cyclohex-2-enes的合成部分…………….…..….21
結論……………………………………………………………………..24
第參章 實驗與儀器……………………………………..………..……25
3-1. 實驗基本條件...…………………………………………………...25
3-2. 溶劑的乾燥…...…………………………………………………...25
3-3. 實驗儀器與測試方法………...…………………………………...26
第肆章 實驗步驟………………………………………………………29
參考資料……………………………..…………………………………53
附圖………………………..………………………………………..…..58

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