本文選題：磺達肝癸鈉　切入點：羥基選擇性保護　出處：《蘇州大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：本論文設(shè)計了一條磺達肝癸鈉重要中間體——單元環(huán)A、C、E的合成新路線�；沁_肝癸鈉是一種選擇性抑制因子Xa的抗凝藥物，它通過非共價鍵與抗凝血酶的活化部位特異性結(jié)合，加速Xa復(fù)合物形成，導(dǎo)致Xa的快速抑制，進而減少凝血酶產(chǎn)生和纖維蛋白形成。磺達肝癸鈉于2001年12月13日獲得EMEA批準，2002年初獲美國FDA批準上市。目前已在法國、英國、德國、中國和美國等國上市，臨床上用于治療和預(yù)防深部靜脈血栓栓塞。 本文設(shè)計的新路線以葡萄糖為起始原料，經(jīng)過乙酰化、1-位對甲苯硫酚取代、去乙�；�4,6-苯甲縮醛保護、3-位選擇性苯甲酰基保護、2-位羥基氧化、選擇性還原，完成葡萄糖構(gòu)型到甘露糖結(jié)構(gòu)的轉(zhuǎn)換，再將羥基轉(zhuǎn)化為疊氮，合成出了單元環(huán)A、C、E可以共用的中間體，該中間體經(jīng)過2至4步的轉(zhuǎn)化合成出單元環(huán)A、C、E環(huán),總共17步反應(yīng)。本文使用葡萄糖合成出了Beta甘露糖硫苷，進而引入疊氮基團生成了關(guān)鍵中間體的方法，，既大大減少了合成此3個單元環(huán)的步驟，也避免了像其他文獻一樣以較貴的甘露糖或氨基葡萄糖為初始原料。
[Abstract]:In this paper, a new route was designed for the synthesis of the important intermediate of fondaparinic sodium, the unit ring Agnocaine E, which is an anticoagulant of selective inhibitory factor Xa, which binds specifically to the activated site of antithrombin by non-covalent bond. Accelerates the formation of Xa complexes, resulting in rapid inhibition of Xa, which in turn reduces thrombin production and fibrin formation. The sodium fondaguein was approved by EMEA in December 13th 2001 and was approved by FDA of the United States in early 2002. It has been approved in France, Britain, Germany, etc. Listed in China and the United States, they are used clinically to treat and prevent deep venous thromboembolism. The new route was designed using glucose as the starting material, substituted by acetylated 1-position p-methylthiophenol, and deacetylated by 4- (4-benzylidene) acetal to protect the 3-position selective benzoyl group to protect 2-position hydroxyl group oxidation and selective reduction. The conversion of glucose configuration to mannose structure was completed, and the hydroxyl group was converted to azide. The intermediate of unit ring Agno Con E was synthesized by 2 to 4 steps of conversion. In this paper, Beta mannose glucosinolate was synthesized using glucose, and the key intermediate was formed by introducing azide group, which greatly reduced the steps of synthesizing these three unit rings. It also avoids starting with more expensive mannose or glucosamine, as in other literature.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R914.5

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