Bervastatin, LS-2904
柏伐他汀Chemical Name: (?-erythro-7-[4-(4-Fluorophenyl)spiro[2H-1-benzopyran-2,1'-cyclopentan]-3-yl]-3,5-dihydroxy-6(E)-heptenoic acid ethyl ester; (?-(3R*,5S*,6E)-7-[4-(4-Fluorophenyl)spiro[2H-1-benzopyran-2,1'-cyclopentan]-3-yl]-3,5-dihydroxyhept-6-enoic acid ethyl ester
CAS No. 132017-01-7
项目整合开发状态: Phase II
项目研究机构: Lipha (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:Derivs.of benzocycloalkenyldihydroxyalkanoic acids,inhibitors of HMG-CoA reductase,antagonists of thromboxane A2 receptors and antifungals
文献作者:Festal,D.; Nioche,J.-Y.; Descours,D.; Bellemin,R.; Decerprit,J.(Lipha Sant?
参考来源:AU 9048797; EP 0380392; FR 2642065; JP 1990258738; US 5082859; US 5183924
📄 详细内容
合成路线: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.
参考文献标题:Bervastatin
文献作者:Festal,D.
参考来源:Drugs Fut 1995,20(12),1217
产品链接: CAS No. 132017-01-7››