A New Approach to the Total Synthesis of Rosuvastatin
作者： Natalia Andrushko , Vasyl Andrushko , Gerd König , Anke Spannenberg , Armin Börner
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摘要: 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-methylmethanesulfonamide (2), was prepared by Pd-catalyzed formylation with CO/H2 (1:1, 50 bar, phosphane ligand/substrate ratio 1:10). Several alternative pathways for preparation 2 were also tested, but found to be inferior. Rosuvastatin precursor 1 assembled Wittig coupling aldehyde and ylide (R)-3, derived from a Ru-catalyzed asymmetric hydrogenation. second stereogenic center finally created stereoselective reduction Et2BOMe NaBH4 afford rosuvastatin ethyl ester. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
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