左炔诺孕酮有关物质的合成  

Synthesis of related substances from levonorgestrel

作　　者：李新鹏[1] 高虎[1] 王冬梅[1] 郑焱 胡彪 吴松[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,卫生部天然药物生物合成重点实验室,北京100050 [2]北京紫竹药业有限公司,北京100024

出　　处：《中国新药杂志》2013年第24期2865-2868,共4页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2011ZX09203-001-16)

摘　　要：目的:合成左炔诺孕酮原料药中的3种有关物质。方法:以左炔诺孕酮为起始原料,将其3位羰基保护得到化合物4,再用半中和的间氯过氧苯甲酸氧化,经分离纯化分别得到有关物质2和3;有关物质2或3经氯铬酸吡啶盐氧化得到有关物质1。结果与结论:合成了左炔诺孕酮原料药中3种有关物质,并经1H NMR,13C NMR和MS等确证结构,纯度经HPLC检测均在98%以上,可以作为左炔诺孕酮原料药质量控制的对照品。Objective： To synthesize three related substances from levonorgestrel. Methods： Started from levonorgestrel, the compound 4 was obtained by protecting 3-carbonyl of the starting material. Oxidation of 4 using the half-neutralized m-chloroperbenzoic acid resulted in the related substances 2 and 3, which were obtained by further isolation and purification, respectively. Then the mixed isomers of 2 and 3 were oxidized by pyridinium chlorochromate to yield related substance 1. Results and conclusion： The three related substances from levonorgestrel were synthesized and verified by 1H-NMR, 13C-NMR and MS. Their purities were over 98% by the detection of HPLC, and they can be used as the reference substances in the quality control of levonorgestrel.

关 键 词：左炔诺孕酮 有关物质 合成 氧化 1H-NMR 

分 类 号：R914.5[医药卫生—药物化学]