臺灣博碩士論文加值系統

中文摘要
色胺酸與各種醛、酮化合物藉Pictet-Spengler反應可以得具多樣化的tetrahydro-β-carboline分子庫。以Pictet-Spengler反應合成tetrahydro-β-carboline時，色胺酸與醛化合物依1：4莫耳比例在室溫下的反應可在一小時內完成，但酮化合物所需反應時間則過於冗長需數週至數月。再者，改變色胺酸與酮化合物為1：12莫耳比例反應時，酮化合物反應時間仍嫌稍長需數日至數週。有鑑於此，色胺酸與酮化合物在1：12莫耳比例下，搭配高效率之微波加熱可明顯縮短反應時間約數分鐘至數小時，同時亦大大改善反應產率使反應條件趨至最適化。
又，在加熱迴流的反應條件下，胺基酸、芳香醛化合物及馬來醯亞胺反應物利用1,3-dipolar 環化加成反應，可合成多樣化的脯胺酸衍生物分子庫。分析利器如高效能液相層析儀（HPLC）及核磁共振光譜儀（NMR）可有效地判斷產物純度及結構。初步實驗結果驗證研究計畫的可行性，此一分子庫的建立及最適化仍有待進一步的探討。

Abstract
Tetrahydro-b-carboline is an important building block for synthesizing various indole and isoquinoline alkaloids, and natural products having the carboline structure often exhibit important medicinal properties. Using the Pictet-Spengler reaction, tryptophan can react with aldehydes and ketones to conveniently afford various substituted tetrahydro-β-carbolines. Under typical experimental conditions, reactions involving aliphatic aldehydes are generally complete in one hour, but aromatic aldehydes and some ketones give slow reaction (hours for aryl aldehydes and days for ketones, respectively) at ambient temperature. In order to increase the diversity of tetrahydro-β-carboline library, an optimized experimental protocol having short reaction time for both aldehydes and ketones is urgently needed. Experimental results presented in this thesis showed that the Pictet-Spengler reaction of ketones with tryptophan is significantly improved when excessive ketone ([ketone] / [tryptophan] = 12) was employed; in the case of 3-pentanone, the reaction was shortened from the original 76.5 days to 5.5 days. Upon incorporation of microwaves, this Pictet-Spengler reaction can be accelerated even further; the 3-pentanone reaction was complete in 3.3 h!
Since the goal of this thesis was to develop the synthesis of cell cycle inhibitors including fumitremorgin C, a library of proline analogues is desired. In short, using 1,3-dipolar several proline derivatives have been prepared and characterized spectrometrically.

章節目錄
第一章 組合化學之簡介 …………………………………001
第二章 利用Pictet-Spengler反應, 從色胺酸（tryptophan）與各 種醛和酮化合物反應可以合成具有取代基的 tetrahydro-β-carboline分子庫合成簡介 ………………008
第一節 藉Pictet-Spengler縮合反應, 進行tetrahydro-β- Carboline分子庫之合成；色氨酸與醛酮依1:4 比例在室溫下合成之結果討論 ………………014
第二節 將第一節反應中的色氨酸與酮依1：12比例在 室溫下合成之結果討論 ………………………022
第三節 將第二節反應中的色氨酸與酮依1：12比例應 用微波加熱法下合成之結果討論 ……………028
第四節 藉Pictet-Spengler縮合反應,進行tetrahydro-β- carboline分子庫之合成之結論 ……………034
第五節 光譜附錄 ………………………………………035
第三章 實驗應用1,3-dipolar cycloaddition反應，再加熱迴流的 條件下, 合成proline衍生物之分子庫 ……………126
第一節 實 驗 …………………………………………130
第二節 結果討論 ………………………………………132
第三節 光譜附錄 ………………………………………133
參考文獻 …………………………………………………………154
附錄 組合化學之簡介 …………………………………………155

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