Bervastatin, LS-2904-药物合成数据库

【药物名称】Bervastatin, LS-2904

化学结构式(Chemical Structure):

参考文献No.	12906
标题:	Derivs. of benzocycloalkenyldihydroxyalkanoic acids, inhibitors of HMG-CoA reductase, antagonists of thromboxane A2 receptors and antifungals
作者:	Festal, D.; Nioche, J.-Y.; Descours, D.; Bellemin, R.; Decerprit, J. (Lipha Sant?
来源:	AU 9048797; EP 0380392; FR 2642065; JP 1990258738; US 5082859; US 5183924

合成路线图解说明: The synthesis of bervastatin is outlined: Heating of 2-hydroxyacetophenone (A) with cyclopentanone (B) and pyrrolidine in toluene gave 3,4-dihydrospiro[1-benzopyran-2(2H),1'-cyclopentan]-4-one (I). 1,2-Addition of 4-fluorophenylmagnesium bromide (D) on (I) followed by dehydration of the intermediate alcohol (II) upon treatment with p-toluenesulfonic acid yielded 4-(4-fluorophenyl)spiro[1-benzopyran-2(2H),1'-cyclopentane] (III). Vilsmeier reaction on (III) using 3-morpholinoacrolein (E) gave the corresponding prop-2-enal (IV). Addition of the dianion of ethyl acetoacetate to aldehyde (IV) and stereospecific reduction of the resulting delta-hydroxy-beta-ketoester (V) with diethylmethoxyborane and sodium borohydride yielded bervastatin.

参考文献No.	329397
标题:	Bervastatin
作者:	Festal, D.
来源:	Drugs Fut 1995,20(12),1217

合成路线图解说明: The synthesis of bervastatin is outlined: Heating of 2-hydroxyacetophenone (A) with cyclopentanone (B) and pyrrolidine in toluene gave 3,4-dihydrospiro[1-benzopyran-2(2H),1'-cyclopentan]-4-one (I). 1,2-Addition of 4-fluorophenylmagnesium bromide (D) on (I) followed by dehydration of the intermediate alcohol (II) upon treatment with p-toluenesulfonic acid yielded 4-(4-fluorophenyl)spiro[1-benzopyran-2(2H),1'-cyclopentane] (III). Vilsmeier reaction on (III) using 3-morpholinoacrolein (E) gave the corresponding prop-2-enal (IV). Addition of the dianion of ethyl acetoacetate to aldehyde (IV) and stereospecific reduction of the resulting delta-hydroxy-beta-ketoester (V) with diethylmethoxyborane and sodium borohydride yielded bervastatin.