期刊
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
卷 2008, 期 5, 页码 847-853出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/ejoc.200700813
关键词
drug design; statins; synthetic methods; homogeneous catalysis; 2-aminopyrimidines; hydroformylation; rosuvastatin
A new multi-step synthesis of the lipid-lowering agent rosuvastatin, involving two homogeneously catalyzed reaction steps, is described. The key building block, N-[4-(4-fluorophenyl)-5-formyl-6-isopropylpyrimidin-2-yl]-N-methylmeth- anesulfonamide (2), was prepared by Pd-catalyzed formylation with CO/H-2 (1:1, 50 bar, phosphane ligand/substrate ratio of 1:10). Several alternative pathways for the preparation of 2 were also tested, but were found to be inferior. Rosuvastatin precursor I was assembled by Wittig coupling of aldehyde 2 and ylide (R)-3, derived from a Ru-catalyzed asymmetric hydrogenation. The second stereogenic center was finally created by stereoselective reduction with Et2BOMe and NaBH4 to afford rosuvastatin ethyl ester. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据