布地奈德产品中杂质A的结构鉴定与合成  

The identification and synthesis of the impurity Ain budesonide

作　　者：晁建平[1] 夏庆[2] 任津岩 王福军[2] 凌仰之[1] 

机构地区：[1]北京大学药学院药物化学系,北京100083 [2]天津药业公司,天津300161

出　　处：《中国药物化学杂志》2006年第2期74-78,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(3017110)

摘　　要：目的鉴定布地奈德产品中含量大于0·1%的杂质A。方法采用闪式柱色谱、HPLC分离得到杂质A,用NMR(1D和2D)及MS测定其化学结构,并设计合成该杂质A以便进一步确证其结构。结果确定了杂质A为16α-丁酰氧基泼尼松龙(1),经HPLC、NMR谱证明合成所得的化合物与分离得到的杂质A完全一致。结论基于所推断的结构,讨论了该杂质A的可能生成途径并改进了合成工艺,从而使其含量小于0·1%。Aim To identify impurity A, the content of which is more than 0.1% in bulk budesonide product. Methods The impurity A was isolated and purified by flash chromatography and HPLC. Its structure was confirmed by spectrometric analysis via 1D and 2D NMR, ESI-MS, the impurity A was synthesized in order to confirm its structure. Results The impuriy A is 16α butanoyloxy prednisolone（1）. The HPLC retention time of impurity A and 16α-butanoyloxy prednisolone as well as ^1H and ^13C-NMR, were totally identical. Conclusion Based on the structure of the impurity A, the possible routes which would form the impurity A were discussed and the preparation process for budesonide was improved to eliminate this impurity A.

关 键 词：药物化学 结构鉴定 化合物合成 16α-丁酰氧基泼尼松龙 

分 类 号：R914[医药卫生—药物化学] O624[医药卫生—药学]