脱氢诺龙醋酸酯的合成工艺研究  

Improved synthesis of dehydronandrolonacetate

作　　者：饶志威[1,2] 左文果[1] 陈登辉[1] 钟大猷[1] 黄红林[2] 李宗桃[1] 

机构地区：[1]武汉大学组合生物合成与新药发现教育部重点实验室,湖北武汉430071 [2]南华大学药物药理研究所,湖南衡阳422101

出　　处：《中国药物化学杂志》2013年第5期368-371,共4页Chinese Journal of Medicinal Chemistry

摘　　要：目的研究脱氢诺龙醋酸酯的合成工艺。方法以雌甾-4-烯-3,17-二酮为起始原料,经醋酸酐酯化、硼氢化钠还原、醋酸酐再酯化、N-溴代丁二酰亚胺(NBS)溴代、脱溴化氢5步反应合成脱氢诺龙醋酸酯。结果与结论目标化合物的结构经1H-NMR、IR谱等确证,总收率由文献报道的51%提高到68.1%。改进后的工艺路线反应条件温和、操作简便、收率高、成本低廉,有利于工业化生产。Dehydronandrolonacetate is a key intermediate for the synthesis of fulvestrant（faslodex） and tibolone,while the former was an anti-breast-cancer drug developed by AstraZeneca Company and the latter was a synthetic steroid marketed by Organone Company for post climacteric complains. In this paper, the dehydronandrolonacetate was obtained from di-19-norandrost-4-ene-3,17-dione via esterification, reduction, acylation, and elimination. The total yield was improved from 51% to 68. 1%. The reaction can become mild and efficient,using indirect anhydride acylation in the synthesis of the key intermediate 3,17/3-diacetoxyl-3,5-estradiene. Compared with the reported process,the proved process is cost-effective, convenient, suitable for indus- trialized production and with higher yield. The structure of the dehydronandrolonacetate was characterized by 1H-NMR and IR.

关 键 词：雌甾4-烯-3 17-二酮 诺龙 脱氢诺龙醋酸酯 工艺优化 

分 类 号：R914[医药卫生—药物化学]