| 摘要 |
PURPOSE: A method for preparing simvastatin is provided, thereby preparing simvastatin under mild condition with no formation of by-products and no additional purification process, so that the yield of simvastatin can be improved. CONSTITUTION: The method for preparing simvastatin represented by formula (1) comprises the steps of: (1) deacylation of lovastatin of formula (2) with inorganic base in alcohol to prepare triol acid of formula (3); (2) reacting the triol acid of formula (3) with halogenated alkyl(or aryl) or dialkylsulfate in the presence of inorganic base to prepare triol acid ester of formula (4); (3) reacting the triol acid ester of formula (4) with dialkyl(or diaryl, arylalkyl) silyldichloride in the presence of base to prepare silyl group-protected silyl ester of formula (5); (4) acylation of the compound of formula (5) with 2,2-dimethylbutyrylchloride to prepare a simvastatin intermediate of formula (6); and (5) deprotecting and cyclizing the simvastatin intermediate of formula (6) in the presence of acid catalyst, wherein R is methyl, ethyl, propyl, normal-butyl, isobutyl, phenylmethyl, or p-methoxyphenylmethyl; and R1 and R2 are the same or different and independently methyl, ethyl, isopropyl, t-butyl or phenyl.
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