本論文之研究目的為利用色胺酸為模板合成含硼色胺酸衍生物並應用於硼中子捕獲治療。以5-Bromo-DL-tryptophan (1)為起始物，進行酸基由甲基保護及胺基受Boc保護，而後以Miyaura borylation反應合成出化合物 (5)，總產率23%。但5-Bromo-DL-tryptophan (1)價格不斐以至於無法大量製備，改以色胺酸 (4)為起始物，進行酸基由甲基保護與胺基受Boc保護後，進行溴化反應，反應並沒有進行，而後不以Boc改用azide保護胺基合成methyl 2-azido-3-(1H-indol-3-yl)propanoate (5)，以NBS可合成出溴化物，接著進行Miyaura borylation反應，卻無得到目標產物 (7)。
利用[Ir(OMe)cod]2催化化合物 (5)合成出(S)-2-azido-3-(2,7-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-3-yl)propanoate (8), methyl (S)-2-azido-3-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-3-yl)propanoate (7)，但產率很低，都只有11%，接著將化合物 (8)水解產生化合物 (9)。
化合物 (8)在細胞累積實驗中，C6-glioma的硼十累積量在2小時達最高，其T/N ratio = 1.3；HuCCT1的硼10累積量在1小時達最高，其T/N ratio = 1.8，而CGCCA的硼10累積量在0和4小時達最高，T/N ratio只有1.0。

The boron-containing amino acid derivatives were synthesized by using tryptophan as template, and applied to boron neutron capture therapy. The compound (5) was synthesized by Miyaura borylation reaction with the 5-Bromo-DL-tryptophan (1) as starting material after the acid group was protected by methylation and the amine group was protected by Boc, and the total yield was 23%. To our convenience, L-tryptophan (4) was employed as the starting material. After the the acid and amine group was protected by methylation and Boc respectively, the reaction was carried out with NBS, but no brominated product was produced. So we didn’t use Boc but azide to protect amine group, and methyl 2-azido-3- (1H-indol-3-yl) propanoate (5) was synthesized. The bromo compound (6) was synthesized by NBS. After Miyaura borylation reaction, the desired product (7) was not obtained.
(S)-2-azido-3-(2,7-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-3-yl)propanoate (8), methyl (S)-2-azido-3-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-3-yl)propanoate (7) were synthzsized from compound (5) by [Ir(OMe)cod]2, but the yield were very slow, only 11% and 11% respectively. The compound (8) is hydrolyzed to provide compound (9).
In the cell accumulation experiment, the accumulation of boron-10 in C6-glioma reached the highest at 2 hours, and its T / N ratio was 1.3; the accumulation of boron-10 in HuCCT1 reached the highest at 1 hour with a ratio of T / N ratio = 1.8, while the accumulation of boron-10 in CGCCA reached the highest at 0 and 4 hours, with a T / N ratio of only 1.0.

第一章 緒論 8
1.1膠質母細胞瘤 8
1.2 硼中子捕獲治療 9
1.3 BNCT臨床用藥以及新發展的硼藥物 11
1.4胺基酸運載體 (amino acid transporter) 14
1.5 LAT1 17
1.6 實驗目的 18
第二章 結果與討論 22
2.1 Miyaura硼化反應 23
2.2 溴化反應 25
2.3 溴化與Iridium硼化反應 27
2.3.1合成methyl (S)-2-azido-3-(2-bromo-1H-indol-3-yl)propanoate (6) 28
2.3.2 嘗試合成methyl (S)-2-azido-3-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-3-yl)propanoate (7) 28
2.3.3 合成methyl (S)-2-azido-3-(2,7-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-3-yl)propanoate (8), methyl (S)-2-azido-3-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-3-yl)propanoate (7) 33
2.4 硼化反應的比較 40
2.5.1 測量化合物 (8)對細胞毒性的結果 43
2.5.1.1化合物 (8)對C6-glioma細胞株的毒性測試 44
2.5.1.2化合物 (8)對fibroblast細胞株的毒性測試 44
2.5.1.3化合物 (8)對CGCCA細胞株的毒性測試 45
2.5.1.4化合物 (8)對HuCCT1細胞株的毒性測試 45
2.5.1.5化合物 (8)對MMNK-1細胞株的毒性測試 45
2.5.2 細胞的硼含量累積實驗 46
第三章 結論 50
第四章 實驗步驟 51
4.1 化學合成步驟 54
4.2 生物實驗步驟 74
4.2.1細胞毒性測試 74
4.2.2細胞的硼含量累積實驗 75
附錄 77
參考文獻 119

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