【摘要】：碳青霉烯類抗生素是一類抗菌能力強、抗菌譜廣的抗生素藥物,現(xiàn)如今這種藥物的應用日益廣泛,同時市場需求量也逐步增長,而這類抗生素并不在自然界中天然存在,不能通過提取的方式獲得,因此這類藥物的化學合成方法廣受關注。 4-AA是一種重要的合成關鍵中間體,是碳青霉烯類抗生素化學全合成的必需原料,因而近年來它的市場價格也在逐步攀升。由于其合成難度大,工業(yè)化生產(chǎn)困難,因此如何低成本、高產(chǎn)率地合成4-AA,已成為碳青霉烯類抗生素開發(fā)的重中之重。 本實驗以L-蘇氨酸為出發(fā)物,經(jīng)過6步反應得到最終產(chǎn)物4-AA。從重氮化反應、C3-C4環(huán)合反應、羥基保護反應、脫保護反應、Baeyer-Villiger氧化反應這五個部分對反應溫度、反應環(huán)境、反應溶劑、催化劑等條件進行優(yōu)化改進,以合理地降低反應成本、提高4-AA的產(chǎn)率,同時提供一條合理可行、綠色環(huán)保、簡捷高效的工業(yè)化生產(chǎn)路線。 改進后得到4-AA的總產(chǎn)率為25.4%,產(chǎn)物重結晶后的純度可達99.5%以上,所得產(chǎn)物通過核磁共振氫譜(1H-NMR)進行了表征,熔點、旋光度也進行了檢驗。
[Abstract]:Carbapenem antibiotics are a class of antimicrobial drugs with strong antibacterial ability and wide antibacterial spectrum. Nowadays, the application of carbapenem is becoming more and more extensive, and the market demand is also increasing, and these antibiotics do not exist naturally in nature. Cannot be obtained by extraction, so the chemical synthesis method of this kind of medicine has attracted much attention. 4-AA is an important intermediate of synthesis, and it is an essential raw material for the chemical synthesis of carbapenem antibiotics. Therefore, the market price of 4-AA has been rising gradually in recent years. It is difficult to synthesize 4-AAs in low cost and high yield, so it has become the most important problem in the development of carbapenem antibiotics. In this experiment, L-threonine was used as the starting material, and the final product 4-AA was obtained after 6 steps of reaction. Diazotization reaction, C3-C4 cyclization reaction, hydroxyl protection reaction, deprotection reaction and Baeyer-Villiger oxidation reaction were optimized and improved under the conditions of reaction temperature, reaction environment, reaction solvent, catalyst and so on. In order to reduce the reaction cost reasonably, improve the yield of 4-AA, and provide a reasonable and feasible, green environmental protection, simple and efficient industrial production route. The total yield of 4-AA was 25.4%, the purity of the product after recrystallization was over 99.5%. The product was characterized by 1H-NMR, and the melting point and optical rotation were also tested.
【學位授予單位】：延邊大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R914

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本文編號：2301123