摘要
本研究改进了地西他滨(1)的合成工艺。将活性炭负载五水四氯化锡固体酸(SnCl4/C)用于催化1合成过程中的乙酰化和糖苷化反应。SnCl4/C代替浓硫酸催化1-O-甲基-2-脱氧-3,5-二-(O-芴甲氧羰基)-D-呋喃核糖(4)合成1-O-乙酰基-2-脱氧-3,5-二-(O-芴甲氧羰基)-D-呋喃核糖(5),能显著提高5的纯度并防止后处理时反应液乳化,5的纯度达到80%以上。SnCl4/C催化5和2-三甲基硅烷氧基-4-三甲基硅烷氨基-1,3,5-三嗪(7)通过糖苷化反应得到1-[3,5-二-(O-芴甲氧羰基)-2-脱氧-α,β-D-核糖]-5-氮杂胞嘧啶(8),反应完毕后过滤即可除去催化剂,8的纯度达到78%以上(α+β),β/α提高至1.3以上。固体酸催化剂重复使用3次后催化效果基本不变。地西他滨的总收率由13%提高至26%。
The synthetic route of decitabine was improved. Catalysis SnCl4·5H2O, which was loaded on activated carbon(SnCl4/C), was applied in the process of acetylation and glycosylation. Concentrated sulfuric acid was instead by SnCl4/C for catalyzing 1-O-methyl-2-deoxy-3,5-bis(O-Fmoc)-D-ribofuranose(4) to prepare 1-acetyl-2-deoxy-3,5-bis(OFmoc)- D-ribofuranose(5), the purity of 5 raised to 80% and the problem of solution emulsified easily also was resolved by this way. The glycosylation was catalyzed by SnCl4/C between 5 and 2-[(trimethylsilyl)amino]-4-[(trimethylsilyl)- oxy]-S-triazine(7) have a marked improvement for the purity of 1-[3,5-bis(Fmoc)-2-deoxyribofuranosyl]-5- azacytidine(8) with 78% purity(α and β), the β/α ratio was at least 1.3. The catalysis efficiency of catalyst unchanged basically after it was used three times. The total yield was increased from 13% to 26%.
作者
赵桂芳
白文钦
郑艺
孙秀玲
张贵民
ZHAO Guifong;BAI Wenqin;ZHENG Yi;SUN Xiuling;ZHANG Guimin(Shandong Newtime Pharmaceutical Co.,Ltd.,Linyi 273400;International Pharmaceutical Engineering Lab.of Shandong Province,Linyi 273400)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2019年第9期972-975,共4页
Chinese Journal of Pharmaceuticals
