2,6-甲氧基氫昆-3-硫醋酸耦合物之有機合成及脢合成反應

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题名:	2,6-甲氧基氫昆-3-硫醋酸耦合物之有機合成及脢合成反應
其它题名:	Organic and Enzymatic Synthesis ofimethoxyhydroquinone
作者:	陳文復 Chen,Wen-Fu
贡献者:	佘亮 Sheh,Leng 東海大學應用化學系
关键词:	2;6-甲氧基氫昆-3-硫醋酸;蛋白脢;2;alcalase;6-dimethoxyhydroquinone(DMQ-MA)
日期:	1993
上传时间:	2011-05-25T08:19:35Z (UTC)
摘要:	本文報告兩組直鏈二胜太和抗癌藥DMQ-MA耦合物的合成。第一組耦合物為: DMQ-MA-Gly-Gly-NH ; DMQ-MA-β-Ala-Gly-NH?; DMQ-MA-Ala-Gly -NH? ; DMQ-MA-Val-Gly-NH?。我們合成這系列耦合物的原因是因為含有 Gly-NH?胺基酸為載體的 DMQ-MA耦合物可增強 DMQ-MA的藥效。第二組耦合物為: DMQ-MA-Gly-Arg-OMe ; DMQ-MA-β-Ala-Arg-OMe; DMQ- MA- Ile-Arg-OMe ; DMQ-MA-Gaba-Arg-OMe。因為癌細胞的細胞表面電價密度會改變。利用Arg-OMe所帶的正電價, 增加DMQ-MA 和癌細胞表面沾黏的能力。另外,嘗試以蛋白脢 alcalase 來催化 DMQ-MA-Ala-OMe; DMQ- MA-Val -OMe; DMQ-MA-Arg-OMe; DMQ-MA-Phe-OMe; 和 Gly-NH,Ala-NH and Phe- NH 的耦合反應,並比較化學法和催化法的產率, 藉以探討 alcalase催化這些反應的選擇性。實驗結果顯示, alcalase的催化反應會受到胺基酸側鏈大小的影響,只有 DMQ-MA-Ala-Gly-NH?和 DMQ-MA-Phe- Gly-NH?能被生成,且產率較化學法低。 This thesis reports the synthesis of two groups of new antitumor drugs which are the conjugates of linear dipeptides and the cyto-toxic agent DMQ-MA。The first group is: DMQ-MA-Gly -Gly-NH?, DMQ-MA-β-Ala-Gly-NH?, DMQ-MA-Ala-Gly-NH?, DMQ-MQ- Val-Gly-NH?。 Since the IC?of DMQ-MA-Gly-NH is 40 times lower than that of DMQ-MA, 120 times lower than that of DMQ-MA-Ala-NH ,thus ,it is logical to synthesize the dipeptides containing Gly-NH?as drug carriers of DMQ-MA。 We also investigate the possibility of using enzymatic reactions for the synthesis of these conjugates。In the enzymatic reactions DMQ-MA-Ala-OMe, DMQ-MA-Val-OMe, DMQ-MA-Phe-OMe and DMQ-MA-Arg-OMe are chosen as acyl donors and Gly-NH ,Ala-NH ,and Phe-NH are nucleophiles。 The enzyme chosen is alcalase。Only DMQ-MA-Ala-Gly-NH?and DMQ- MA-Phe-Gly-NH? can be sucessfully synthesized by the alcalase method, and the yield is lower than that of organic synthesis。 The second group is DMQ-MA-Gly-Arg-OMe, DMQ-MA-β -Ala-Arg-OMe, DMQ-MA-Gaba-Arg-OMe and DMQ-MA-Ile-Arg-OMe。 Since the charge density of malignant cell surface is different from that of normal cells , the peptides containing positive charge amino acid like Arg may bind to malignant cells more efficiently than DMQ-MA itself.
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