Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
R&D Department, Esteve Química S.A., Caracas 17-19, 08030 Barcelona, Spain.
Molecules. 2020 Nov 30;25(23):5644. doi: 10.3390/molecules25235644.
A catalytic and enantioselective preparation of the ()-4-methyleneproline scaffold is described. The key reaction is a one-pot double allylic alkylation of an imine analogue of glycine in the presence of a chinchonidine-derived catalyst under phase transfer conditions. These 4-methylene substituted proline derivatives are versatile starting materials often used in medicinal chemistry. In particular, we have transformed -butyl ()-4-methyleneprolinate () into the -Boc-protected 5-azaspiro[2.4]heptane-6-carboxylic acid (), a key element in the industrial synthesis of antiviral ledipasvir.
描述了（）-4-亚甲基脯氨酸骨架的催化和对映选择性制备方法。关键反应是在相转移条件下，在手性金鸡纳碱衍生催化剂的存在下，甘氨酸亚胺类似物的一锅法双烯丙基烷基化。这些 4-亚甲基取代的脯氨酸衍生物是在药物化学中常用的多功能起始材料。特别是，我们将叔丁基（）-4-亚甲基脯氨酸酯（）转化为 Boc 保护的 5-氮杂螺[2.4]庚烷-6-羧酸（），这是抗病毒药物 ledipasvir 工业合成中的关键元素。
