本文選題：抗糖尿病藥物　切入點(diǎn)：二肽基肽酶-IV　出處：《天津理工大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：近年來(lái)全球Ⅱ型糖尿病患者人數(shù)呈逐年上升的趨勢(shì)，已成為同心腦血管疾病和癌癥一樣嚴(yán)重危害人類健康的疾病。DPP-4抑制劑是最具前景的抗Ⅱ型糖尿病藥物。DPP-4抑制劑維格列汀作為諾華公司研發(fā)的抗糖尿病新型口服藥，有其巨大的市場(chǎng)價(jià)值和科研意義。 論文在總結(jié)和研究前人所做相關(guān)工作的基礎(chǔ)上，，為適合工業(yè)化大生產(chǎn)的安全性和可操作性，對(duì)維格列汀的合成工藝進(jìn)行了優(yōu)化。本路線以廉價(jià)的L-脯氨酸為起始原料，無(wú)需催化劑，與活潑的氯乙酰氯發(fā)生酰胺化反應(yīng)，生成(S)-1-(2-氯乙�；�)-2-吡咯烷甲酸，此化合物中的甲酸基團(tuán)采用氨基磺酸作為脫水劑，脲素為氨源，使用分段保溫一步法成氰，得到中間體（S）-1-（2-氯乙�；�-2-腈基吡咯烷；合成中間體3-氨基-1-金剛烷醇時(shí)，采用3-氨基-1-金剛烷胺為原料，硝酸鈉與硫酸作為硝化劑，硼酸為催化劑進(jìn)行硝化反應(yīng)，然后用氫氧化鉀親核取代得到3-氨基-1-金剛烷醇；再將(S)-1-(2-氯乙�；�)-2-吡咯烷甲酸和3-氨基-1-金剛烷醇反應(yīng)，以碘化鉀為催化劑，無(wú)水碳酸鉀為縛酸劑得到維格列汀。本實(shí)驗(yàn)還合成了部分維格列汀雜質(zhì)。所得目標(biāo)化合物均使用熔點(diǎn)測(cè)定，IR，1HNMR，MS，元素分析等方法確證其結(jié)構(gòu)，并對(duì)維格列汀做了粉末衍射確認(rèn)晶型。此工藝路線提高了產(chǎn)品總收率，達(dá)到47.7%。
[Abstract]:In recent years, the number of type 2 diabetes patients in the world is increasing year by year. The DPP-4 inhibitor is the most promising antidiabetic drug. DPP-4 inhibitor is a new oral antidiabetic drug developed by Novartis. Has its huge market value and scientific research significance. On the basis of summarizing and studying the related work done by predecessors, in order to adapt to the safety and maneuverability of large-scale industrial production, the synthesis process of vieglentin was optimized. This route starts with cheap L-proline as the starting material. No catalyst was needed to amidation the active chloroacetyl chloride to form a formic acid, which contained amino sulfonic acid as dehydrating agent and urea as ammonia source to form cyanide by one-step thermal insulation, and the formic group in the compound was formed by one-step method. The amino sulfonic acid was used as dehydrating agent, and urea was used as ammonia source, and the amidation reaction was carried out with active chloroacetyl chloride. The intermediate was synthesized by using 3-amino-1-amantadine as raw material, sodium nitrate and sulfuric acid as nitration agent, and boric acid as catalyst for nitration, and the intermediate was synthesized by using 3-amino-1-adamantanol as raw material, sodium nitrate and sulfuric acid as nitration agent, and boric acid as catalyst for the nitration of pyrrolidine. Then, 3-amino-1-adamantanol was synthesized by nucleophilic substitution of potassium hydroxide, and then reacted with 3-amino-1-adamantanol, and then reacted with 3-amino-1-adamantanol, and was catalyzed by potassium iodide. In this experiment, some impurity of Veglentin was synthesized. The target compounds were characterized by melting point determination, elemental analysis and elemental analysis. The crystal form was confirmed by powder diffraction, and the total yield of the product was increased to 47.7%.
【學(xué)位授予單位】：天津理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R914.5

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