布地奈德杂质16,17-脱氢-21-羟基泼尼松龙的合成  

Synthesis of Budesonide Impurity 16,17-Dehydro-21-hydroxy Prednisolone

作　　者：刘彦龙 蔡正贵 张健青 郭亚辉 聂全登 杨列超 胡中元 LIU Yan-long;CAI Zheng-gui;ZHANG Jian-qing;GUO Ya-hui;NIE Quan-deng;YANG Lie-chao;HU Zhong-yuan(Research Institute of Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.,Nanjing 210000,China)

机构地区：[1]正大天晴药业集团股份有限公司研究院,江苏南京210000

出　　处：《精细化工中间体》2025年第1期38-41,共4页Fine Chemical Intermediates

摘　　要：为有效控制布地奈德原料药质量并建立质量标准,以21-羟基孕甾-1,4,9(11),16-四烯-3,20-二酮-21-醋酸酯(■)为起始原料,经NBS溴代,在锌粉和六水合三氯化铬的作用下脱溴,再利用脂肪酶脱去乙酰基制得布地奈德杂质16,17-脱氢-21-羟基泼尼松龙(■),并优化了合成工艺。同时其结构经^(1)H NMR、^(13)C NMR和HRMS确证。杂质总收率57.2%(以■计),纯度98.7%(HPLC法)。合成工艺合理、原料易得、反应条件温和,制备的杂质纯度高,可作为布地奈德杂质对照品用于质量研究。To effectively control the quality of Budesonide and establish comprehensive quality standards,the synthesis of a Budesonide impurity was undertaken.The starting material,3,20-dioxopregna-1,4,9(11),16-tetraen-21-yl acetate (■),was subjected to a series of chemical transformations.First,bromination was performed using N-bromosuccinimide (NBS),followed by debromination in the presence of zinc powder and chromium trichloride hexahydrate.Finally,deacetylation was carried out using lipase,yielding the Budesonide impurity 16,17-dehydro-21-hydroxy prednisolone (■).This process achieved a high overall yield of approximately 57.2%(based on compound■) and a purity of 98.7%as determined by HPLC.The structural identity of the impurity was confirmed through detailed spectroscopic analyses,including ^(1)H NMR,^(13)C NMR,and HRMS.Process optimization ensured mild reaction conditions,making the synthesis both practical and efficient.The high purity of the resulting impurity makes it suitable as a reference standard for the quality control of Budesonide.

关 键 词：布地奈德 脂肪酶 杂质 

分 类 号：TQ460[化学工程—制药化工]