Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3118
標題: 磷酸催化N-乙醯-D-葡萄醣胺和N-乙醯-D-甘露醣胺的差向異構反應
Phosphate-catalyzed epimerization of N-acetyl-D-glucosamine and N-acetyl-D-mannosamine
作者: 林盟凱
Lin, Meng-Kai
關鍵字: N-乙醯-D-葡萄醣胺;N-acetyl-D-glucosamine;N-乙醯-D-甘露醣;磷酸催化;N-acetyl-D-mannosamine;Phosphate-catalyzed
出版社: 化學工程學系所
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摘要: 
唾液酸(sialic acid)是合成許多藥物的重要前驅物,如抗流感病毒藥物。在唾液酸的製程中為了降低生產成本,因而提出了使用價格較低的N-acetyl-D-glucosamine (GlcNAc)經由鹼性條件下或GlcNAc 2-epimerase異構化生成N-acetyl-D-mannosamine (ManNAc),再利用Neu5Ac aldolase催化和添加pyruvate合成唾液酸的二階段製程法;然而本實驗室在偶然間發現利用磷酸並且在高溫情況下也可以使GlcNAc異構化生成ManNAc。
本研究主要探討在磷酸催化下,其動力學和熱力學上的參數討論,更進一步運用於連續式操作上。使用磷酸當作催化劑下,GlcNAc的催化過程為一次反應,而速率常數隨著反應溫度和磷酸濃度的上升而增加,但當磷酸濃度達到500 mM即為催化劑的飽和濃度;在高溫和高磷酸濃度的批次反應情況下,GlcNAc的平衡轉換率約有31%,平衡常數為0.45;其平衡轉換率及平衡常數皆比使用GlcNAc 2-epimerase當作催化劑來的高一些。
在熱力學參數方面,磷酸催化反應的自由能變化量為2.32 kJ/mole,反應熵為1.83 kJ/mole,反應所需的活化能為56.36 kJ/mole。在連續式攪拌反應器操作下,當τ(space time)為250小時可達到最大的平衡轉換率,約為29%。

Sialic acid is a precursor for the manufacture of many pharmaceutical drags, such as anti-influenza virus agents. In order to reduce the cost of substrate (ManNAc), a two-step process under alkaline condition or with GlcNAc 2-epimerase epimerize N-acetyl-D-glucosamine (GlcNAc) to N-acetyl-D-mannosamine (ManNAc), and then add the pyruvate with the N-acetyl-D-neuraminic acid (Neu5Ac) aldolase-catalyzed has been proposed, enabling using the relatively inexpensive GlcNAc, as the starting reactant. By accident, we find that use phosphates as the catalyst also can epimerize N-acetyl-D-glucosamine in high temperature.
In this thesis, we research the kinetic and the thermodynamic parameters in phosphate-catalyzed epimerization, and then using the parameters in continuous stirred tank reactor (CSTR). Under using phosphates as the catalyst, it is the first-order reaction. The rate constant is increasing with reaction temperature and phosphate concentration. When the phosphate concentration reaches 500 mM is the saturated point as catalyst. In the batch reactor under high temperature and phosphate concentration condition, the conversion of GlcNAc is about 31%, and the equilibrium constant is 0.45; consequently, they are higher than using the GlcNAc 2-epimerase as catalyst.
In the thermodynamics of phosphate-catalyzed reaction, the free energy change is 2.32 kJ/mole, and the reaction of enthalpy change is 1.83 kJ/mole, and activation energy is 56.36 kJ/mole. The effect of space time on conversion in a CSTR will be discussed. The conversion of GlcNAc is the maximum, about 29%, when space time reaches 250h.
URI: http://hdl.handle.net/11455/3118
其他識別: U0005-3107201210041100
Appears in Collections:化學工程學系所

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