臺灣博碩士論文加值系統

人參是五加科（Araliaceae）多年生植物 Panax ginseng C. A. Meyer 之乾燥根，主產於我國東北及朝鮮半島，自古以來一直被視為珍貴之補劑。神農本草經將其列為上品，有補五臟，安精神，止驚悸，明目益智之功效。雖然人參已經使用了數千年，但直到1960年代它的化學成份才逐漸被分離出來；到了1980年代，在天然物中較不尋常的polyacetylene類化合物從人參中分離出來，具有抗腫瘤活性及細胞毒性，這些化合物基本上都是含有十七個碳的1,3-diynol，而panaxydol是其中之一，本論文主要是從事其合成之研究，以更確認其立體結構。
我們以propenal為起始物，和trimethylsilylacetylene反應，經減壓蒸餾後與N-bromosuccinimide和AgNO3在室溫下反應即可得到一bromoacetylene。另外再以trans-2-decenal為起始物，經過DIBAL-H的還原反應，再用PBr3轉換成allyl bromde，與AD-mix-α進行Sharpless asymmetric dihydroxylation並環化形成epoxy化合物。然後用TBDMSCl保護OH基，和trimethylsilylacetylene反應後再將C-4上之OH基和methanesulfonyl chloride反應形成mesylate，再加入TBAF除去保護基，並環化形成(4R,5S)-4,5-epoxy-1-dodecyne。最後若再與5-bromo-1-penten-4-yn-3-ol利用copper(I) iodide在pyrrolidine中反應，進行coupling之後，將可以獲得具有3R,9R,10S和3S,9R,10S結構之panaxydol。
除了合成5-bromo-1-penten-4-yn-3-ol以外，本論文完成了合成panaxydol最主要之先驅物 (4R,5S)-4,5-epoxy-1-dodecyne之合成，將有助於人參中其他epoxy polyacetylene化合物之合成。

Panax ginseng was use in traditional Chinese medicine for a long time as a general tonic and cardiotonic. Systematic pharmacological investigations revealed a multifaceted biological activity of ginseng, including effects on the cardiovascular, immune, and nervous systems, and activity as an antidote, antitumor agent, or antitumor adjuvant and as an antidiabetic. Although Panax ginseng has already been commonly used for thousands of years, its chemical constituents was only gradually isolated and characterized in the 1960s. In the 1980s, some quite unusual chemical components with polyacetylene group were isolated from Panax ginseng and showed to suppress the in vitro growth of cultured tumor cells. These components containing 17 carbons were known as 1,3-diynol, and panaxydol is one of these components. In this thesis, the synthesis of panaxydol with an asymmetric method was investigated.
We started with trans-2-decenal, which was reduced to trans-2- decen-1-ol by DIBAL-H. Phosphorus tribromide transformed the alcohol into an ally1 bromde, and the bromide was converted into the epoxy alcohol through Sharpless asymmetric dihydroxylation with AD-mix-α. The hydroxyl group was protected with TBDMSCl and trimethylsilyl- acetylene reacted with the epoxide in the presence of BF3‧Et2O to produce an acetylene alcohol. The hydroxyl group was converted into the mesylate by treatment with methanesulfony1 chloride. Then, TBAF removed the silyl protecting group and cyclized to displace mesylate ion to afford (4R,5S)-4,5-epoxy-1-dodecyne. In addition, propenal was reacted with lithium trimethylsilylacetylide to give the addition product, which was transformed into the bromoacetylene with N-bromo- succinimde and AgNO3. Finally, if the bromoacetylene couples with (4R,5S)-4,5-epoxy-1-dodecyne using Cadiot-Chodkiewicz procedure, panaxydol will be obtained, which has the configuration of 3R,9R,10S and 3S,9R,10S.
In this synthetic study of panaxydol, 5-bromo-1-penten-4-yn-3-ol and (4R,5S)-4,5-epoxy-1-dodecyne were successfully synthesized. The latter is an important precursor for the synthesis of panaxydol, andits synthesis provides a good synthetic route for the other epoxy acetylenes in Panax ginseng.

摘要--------------------------------------------i
英文摘要--------------------------------------iii
壹、緒論
1-1植物簡介-------------------------------------1
1-2研究動機與目的-------------------------------2
1-3歷史回顧-------------------------------------5
貳、儀器材料------------------------------------7
參、藥品試劑------------------------------------8
肆、研究方法-----------------------------------12
伍、實驗步驟-----------------------------------14
陸、結果與討論---------------------------------38
柒、參考文獻-----------------------------------50
捌、附錄---------------------------------------52

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