合成氮上具取代基的麩胺酸衍生物作為海人草酸生物合成研究的前驅物
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2021
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['Prekainic acid為kainic acid生物合成的重要前驅物，為了研究kainic acid生物合成路徑的反應機制，本實驗透過有機合成獲得prekainic acid及其衍生物，包含不同碳鏈長度的衍生物，以及雙鍵環境不同的衍生物，提供張瑋成教授團隊進行部分的生物測試實驗。\n本實驗以自行製備的dimethyl L-glutamate作為起始物，進行氮上取代反應，但是在去除甲酯保護基的步驟容易影響氮上之取代基，導致副產物的生成且無法進行純化，因此我們改以市售試劑L-glutamic acid di-tert-butyl ester hydrochloride作為起始物。我們嘗試於氮上建立不同取代基，並利用市售可得試劑，分別使用reductive amination、SN2 reaction於氮上建立取代基。另外，我們使用dimethyl L-glutamate進行氮上保護基的篩選，經測試後我們使用4- nitrobenzenesulfonyl作為氮上保護基，並順利地利用Mitsunobu alkylation於胺上進行烷基化反應。\n獲得氮上取代產物後，我們使用鹽酸水溶液進行tert-butyl保護基的水解反應，成功合成prekainic acid衍生物。部分衍生物會產生副產物且無法使用管柱層析法純化，則參考張瑋成教授團隊之條件，改以三氟乙酸 (TFA)進行 tert-butyl 保護基的水解反應，並使用NMR核磁共振光譜對反應進行追蹤。\n最終我們成功的使用較低當量數的三氟乙酸進行反應，獲得高純度之prekainic acid及其衍生物，提供張瑋成教授團隊進行後續的生物測試實驗。\n']
["Prekainic acid is an important precursor of kainic acid biosynthesis. In order to study the reaction mechanism of kainic acid biosynthesis pathway, this experiment obtained prekainic acid and its derivatives through organic synthesis, including derivatives with different carbon chain lengths and different double bond environments derivatives. Finally, provided these derivatives to team for Professor Wei-Chen, Chang to conduct parts of the biological test.\nThis experiment uses self-prepared dimethyl L-glutamate as the starting material to carry out the substitution reaction on the nitrogen, but the step of removing the methyl ester protecting group easily affects the substituents on the nitrogen, resulting in the formation of by-products and cannot be purified. Therefore, we use commercially available reagent L-glutamic acid di-tert-butyl ester hydrochloride as the starting material. We tried to establish different substituents on the nitrogen, and used commercially available reagents to establish the substituents on the nitrogen using reductive amination and SN2 reaction, respectively. In addition, we use dimethyl L-glutamate to screen the nitrogen protecting group. After testing, we use 4-nitrobenzenesulfonyl as the nitrogen protecting group and successfully use Mitsunobu alkylation to carry out the alkylation reaction on the amine.\nAfter obtaining the nitrogen substitution product, we used hydrochloric acid aqueous solution to hydrolyze the tert-butyl protecting group, and successfully synthesized the prekainic acid derivative. Some derivatives will produce by-products and cannot be purified by column chromatography. According to the conditions of Professor Wei-Chen, Chang’s team, use trifluoroacetic acid (TFA) to carry out the hydrolysis reaction of tert-butyl protecting group, and use NMR nuclear magnetic resonance spectroscopy to responses are tracked.\nIn the end, we successfully used trifluoroacetic acid with a lower equivalent number for the reaction to obtain high-purity prekainic acid and its derivatives, and provided Professor Wei-Chen, Chang's team for subsequent biological test experiments.\n"]
["Prekainic acid is an important precursor of kainic acid biosynthesis. In order to study the reaction mechanism of kainic acid biosynthesis pathway, this experiment obtained prekainic acid and its derivatives through organic synthesis, including derivatives with different carbon chain lengths and different double bond environments derivatives. Finally, provided these derivatives to team for Professor Wei-Chen, Chang to conduct parts of the biological test.\nThis experiment uses self-prepared dimethyl L-glutamate as the starting material to carry out the substitution reaction on the nitrogen, but the step of removing the methyl ester protecting group easily affects the substituents on the nitrogen, resulting in the formation of by-products and cannot be purified. Therefore, we use commercially available reagent L-glutamic acid di-tert-butyl ester hydrochloride as the starting material. We tried to establish different substituents on the nitrogen, and used commercially available reagents to establish the substituents on the nitrogen using reductive amination and SN2 reaction, respectively. In addition, we use dimethyl L-glutamate to screen the nitrogen protecting group. After testing, we use 4-nitrobenzenesulfonyl as the nitrogen protecting group and successfully use Mitsunobu alkylation to carry out the alkylation reaction on the amine.\nAfter obtaining the nitrogen substitution product, we used hydrochloric acid aqueous solution to hydrolyze the tert-butyl protecting group, and successfully synthesized the prekainic acid derivative. Some derivatives will produce by-products and cannot be purified by column chromatography. According to the conditions of Professor Wei-Chen, Chang’s team, use trifluoroacetic acid (TFA) to carry out the hydrolysis reaction of tert-butyl protecting group, and use NMR nuclear magnetic resonance spectroscopy to responses are tracked.\nIn the end, we successfully used trifluoroacetic acid with a lower equivalent number for the reaction to obtain high-purity prekainic acid and its derivatives, and provided Professor Wei-Chen, Chang's team for subsequent biological test experiments.\n"]
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