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目的改进新型降血脂药辛伐他汀(simvastatin)的合成工艺。方法以洛伐他汀(lovastatin)为起始原料,经酰胺化、选择性酯化、碳负离子形成、甲基化、水解、中和与环合等反应制得辛伐他汀。结果与结论目标化合物的结构经元素分析、IR、UV、1H-NMR1、3C-NMR及MS谱确证,辛伐他汀的质量符合国内外药典标准,总收率为84.3%。新工艺路线用氯甲酸甲酯替代有机氯硅烷保护羟基,不仅解决了传统工艺中有机氯硅烷脱保护后生成的产物有机硅醇和溶剂甲醇不能循环利用的问题,而且省去了脱有机硅保护基的酸水解和产品精制过程,原料成本显著降低。
Objective To improve the synthesis of simvastatin, a new hypolipidemic drug. Methods Starting from lovastatin, simvastatin was prepared by amidation, selective esterification, formation of carbanion, methylation, hydrolysis, neutralization and cyclization. Results and Conclusions The structure of the target compound was confirmed by IR, UV, 1H-NMR1,3C-NMR and MS spectra. The quality of simvastatin conformed to the standards of Pharmacopoeia at home and abroad with a total yield of 84.3%. The new process route replaces organochlorosilanes with hydroxymethyl chloroformates to protect the hydroxyl groups, which not only solves the problem that organosilanes and solvent methanol, which are the products of the organochlorosilane deprotection in the traditional process, can not be recycled, but also eliminates the need to remove the organosilicon protecting groups Acid hydrolysis and product refining process, raw material costs significantly reduced.