A new approach to the total synthesis of rosuvastatin
A new approach to the total synthesis of rosuvastatin
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DOI：
10.1002/ejoc.200700813
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发表时间：
2008-02-01
影响因子：
2.8
通讯作者：
Boerner, Armin
中科院分区：
文献类型：
--
作者：
Andrushko, Natalia;Andrushko, Vasyl;Boerner, Armin
介绍了一种新的多步合成降脂药瑞舒伐他汀的方法，包括两个均相催化反应步骤。关键结构单元N-[4-（4-氟苯基）-5-甲酰基-6-异丙基嘧啶-2-基]-N-甲基甲磺酰胺（2）是通过Pd催化的与CO/H-2（1：1，50巴，膦配体/底物比为1：10）的反应制备的。还测试了制备2的几种替代途径，但发现其较差。瑞舒伐他汀前体I通过醛2和叶立德（R）-3的Wittig偶联组装而成，叶立德（R）-3来自Ru催化的不对称氢化。第二个立体中心最终通过Et 2BOMe和NaBH 4的立体选择性还原产生，得到瑞舒伐他汀乙酯。((c)Wiley-VCH Verlag GmbH & Co. KGaA，69451魏因海姆，德国，2008）。
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).