本文選題：WS + 雜質(zhì)合成��； 參考：《中國新藥雜志》2015年10期

【摘要】：目的:為推進新型降血脂候選藥物WS070117的臨床前研究,合成其雜質(zhì)對照品以便對原料藥進行質(zhì)量控制。方法:碳酸鉀對原料藥直接水解可得到雜質(zhì)A;水合肼對腺苷中核糖片段的乙酰基進行選擇性水解,得到雜質(zhì)B或者雜質(zhì)C和D兩組分固定比例的混合物;從6-氯腺苷出發(fā),利用三苯基甲基作為保護基,合成雜質(zhì)E;利用不同位置乙�；a(chǎn)物1H NMR的酰化位移確定目標(biāo)產(chǎn)物的結(jié)構(gòu)。結(jié)果:合成了雜質(zhì)A,B,C和D的混合物以及雜質(zhì)E。結(jié)論:確定了腺苷核糖片段乙�；獾乃俾蕿镺-2'O-3'O-5',發(fā)現(xiàn)了O-2'和O-3'位之間乙酰基遷移現(xiàn)象,加酸可以減緩乙�；w移的速率,同時抑制O-3'向O-2'位的遷移。
[Abstract]:Aim: to promote the preclinical study of WS070117, a new candidate drug for lowering blood lipid, to synthesize its impurity reference substance and to control the quality of the drug. Methods: the impurity A was obtained by direct hydrolysis of potassium carbonate to the raw material, and the acetyl group of ribose fragment in adenosine was selectively hydrolyzed by hydrazine hydrate to obtain impurity B or a mixture of impurity C and D in a fixed proportion. The impurity E was synthesized by using triphenyl methyl as the protective group, and the structure of the target product was determined by the acylation shift of the acetylated product 1H NMR at different positions. Results: the mixture and impurity E were synthesized. Conclusion: the rate of acetyl hydrolysis of adenosine ribose fragment was determined to be O-2O3 (O-5N). The phenomenon of acetyl migration between O-2'and O-3'sites was found. The addition of acid could slow the rate of acetyl migration and inhibit the migration of O-3'to O-2'site.
【作者單位】： 中國醫(yī)學(xué)科學(xué)院北京協(xié)和醫(yī)學(xué)院藥物研究所活性物質(zhì)的發(fā)現(xiàn)與適藥化研究北京市重點實驗室;
【基金】：國家“十二五重大新藥創(chuàng)制”科技重大專項:新結(jié)構(gòu)類型調(diào)血脂化合物WS070117臨床前研究(2012ZX09102101-020)
【分類號】：R914.5

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1 連澤勤;朱海波;;探討化合物WS070117調(diào)血脂靶點及相互作用機制[A];全國第十二屆生化與分子藥理學(xué)學(xué)術(shù)會議論文集[C];2011年

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