臺灣博碩士論文加值系統

我們利用DCC以逐步偶合的方式合成Tyr-Ile-Gln-AsnOMe的片段。首先是以( CH3 )2SO4將Cbz-Asn甲基化，之後氫化去Cbz，再與Cbz-Gln偶合，形成Cbz-Gln-AsnOMe；接著再次氫化，可獲得Gln-AsnOMe的片段。另一方面，Ile-OBn以DCC與Boc-Tyr反應形成Boc-Tyr-Ile-OBn，隨後氫化可得到Boc-Tyr-Ile。將這兩個片段以DCC偶合後再以TFA去除Boc保護基就可以得到Tyr-Ile-Gln-AsnOMe。另一邊的五太片段則是以(Boc-Cys)2 與Pro-Leu-GlyNH2以DCC為偶合劑，形成(Boc-Cys)2-Pro-Leu-GlyNH2，再以TFA將保護基去掉，形成(Cys)2-Pro-Leu-GlyNH2。
利用木瓜酵素催化酯化反應，以甲醇於乙酸乙酯中將(Boc-Cys)2形成不對稱的單酯是可行的。反應在pH = 4.2，及於25℃的狀態下震盪進行，而使用榕樹酵素則可獲得高達94.1％之單取代的酯類。
我們將Tyr-Ile-GlnOMe與(Boc-Cys)2OMe以DCC偶合，並未成功，而將(Cys)2-Pro-Leu-GlyNH2與Boc-Asn，以thermolysin加以催化偶合，所得到的產物尚未鑑定出。將五太及四太以DIC加熱迴流無法偶合，而以diazomethane酯化(Boc-Cys)2-Pro-Leu-GlyNH2，結果則是沒有反應。總而言之，我們使用這些方法仍未能成功的形成九太。

The segment, Tyr-Ile-Gln-AsnOMe, was synthesized by a stepwise method using DCC. Cbz-Asn was reacted with dimethyl sulfate to form Cbz-AsnOMe, which was hydrogenated to remove the Cbz group. The resulting compound was then coupled with Cbz-Gln to form Cbz-Gln-AsnOMe, which was hydrogenated to obtain Gln-AsnOMe. On the other hand, Boc-Tyr was condensed with Ile-OBn by DCC, followed by hydrogenation to from Boc-Tyr-Ile. Coupling of Boc-Tyr-Ile with Gln-AsnOMe subsequently and removal of the Boc group by TFA gave Tyr-Ile-Gln-AsnOMe. The other segment, (Boc-Cys)2-Pro-Leu-GlyNH2, was obtained by coupling (Boc-Cys)2 and Pro-Leu-GlyNH2with DCC, followed by deprotection with TFA to from (Cys)2-Pro-Leu-GlyNH2.
Papain catalyzed esteritication of (Boc-Cys)2 with methanol in ethyl acetate to from unsymmetric cystine monoester was doable. The reactions were performed at pH 4.2 and shaked at 25℃. However, cystine monoester was afforded in the yield of 94.1％, if ficin was used.
Direct coupling of (Boc-Cys)2OMe and Tyr-Ile-Gln-AsnOMe with DCC was not successful. Coupling of (Cys)2-Pro-Leu-GlyNH2 and Boc-Asn with thermolysin was attemped, but the resulting compound was not characterized. The coupling of the pentapeptide with tetrapeptide by DIC in reflux was not successful. No reaction was occurred upon esterification of (Boc-Cys)2-Pro-Leu-GlyNH2 with diazomethane. Therefore, we were unable to from nonapeptide with these methods.

第一章、 序論 1
第二章、 文獻探討 2.1 胜太鍵的形成 3
2.2 官能基的保護與去保護 5
2.3 反應的消旋化 7
2.4 合成策略 8
2.5 合成技術 9
2.6 催產素合成發展史 11
第三章、 研究內容
3.1 液相合成法 13
3.1.1 Cbz-Asn-OMe之合成 14
3.1.2 Asn-OMe之合成 15
3.1.3 Cbz-Gln-Asn-OMe之合成 16
3.1.4 Gln-Asn-OMe之合成 18
3.1.5 TsOH-Ile-OBn之合成 19
3.1.6 Ile-OBn之製備 20
3.1.7 Boc-Tyr-Ile-OBn之合成 21
3.1.8 Boc-Tyr-Ile-OH之合成 22
3.1.9 Boc-Tyr-Ile-Gln-Asn-OMe之合成 24
3.1.10 Tyr-Ile-Gln-Asn-OMe之合成 25
3.1.11 (Boc-Cys)2-Pro-Leu-Gly-NH2之合成 26
3.1.12 Cys-Cys-Pro-Leu-Gly-NH2之合成 28
3.1.13 Boc-Cys-Pro-Leu-Gly-NH2之合成
Boc-Cys-OMe 30
3.1.14 (Boc-Cys)2-OMe之合成 34
3.1.15 (Boc-Cys)2-Tyr-OMe之合成 39
3.1.16 (Boc-Cys)2-Pro-Leu-Gly-NH2的酯化 42
3.2 酵素催化法 3.2.1 (Boc-Cys)2-OMe之合成 43
3.2.2 Boc-Asn-Cys-Pro-Leu-Gly-NH2之合成 44
Cys
3.2.3 不同酵素對合成(Boc-Cys)2-OMe的影響 44
3.2.4 不同條件對合成(Boc-Cys)2酯類的影響 45
藥品與儀器設備 47
第四章、 結論與展望 51
第五章、 參考文獻 54

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10. Bodanszky, M. "Principles of Peptide Synthesis" 1984
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