A modified synthetic route of simvastatin
Lihui Duan · Zhongguo yaowu huaxue zazhi · 2010
Aim To improve the synthetic process of simvastatin,a new cholesterol-lowering drug.Methods Simvastatin was synthesized via acetylization,selective esterification,carbanion formation,methylation,hydrolyzation,neutralization and cyclization starting from lovastatin.Results and conclusion The target compound structure was identified by elementary analysis,infra-red spectrum,ultra-violet spectrum,1H-NMR spectrum,13C-NMR spectrum and MS spectrum.The raw materials′ cost is significantly reduced in this novel synthetic process and the product of simvastatin with a overall yield of 84.3%,which conforms to internal and external pharmacopedia specifications.Methyl chloroformate in stead of organochlorosilane was used to protect hydroxyl.It not only solved the problem for conventional process in which the solvent containing organosilicon alcohol originated from organochlorosilane can not be recycled,but also abolished acid hydrolysis for deprotection and purification of crude product as well.