López-Pérez Borja, Maestro Miguel A, Mouriño Antonio
Departamento de Química Orgánica, Laboratorio de Investigación Ignacio Ribas, Universidad de Santiago de Compostela, Avda. Ciencias s/n, 15782 Santiago de Compostela, Spain.
Chem Commun (Camb). 2017 Jul 18;53(58):8144-8147. doi: 10.1039/c7cc04690a.
Herein, we describe a versatile and efficient total synthesis of 1α,25-dihydroxyvitamin D (calcitriol). The synthetic strategy relies on an unprecedented Si-assisted S2'-syn displacement of carbamates by cuprates to set the challenging pivotal quaternary methyl group at the fused-ring junction of the CD-trans-hydrindane core. Other key transformations involve the catalytic asymmetric reduction of an α,β,γ,δ-unsaturated ester with CuH to generate the natural steroidal configuration at C20 and a Pauson-Khand cyclization to form the CD-ring skeleton. This strategy enables the syntheses of novel analogs for structure-function studies and drug development.
在此，我们描述了一种通用且高效的1α,25 - 二羟基维生素D（骨化三醇）的全合成方法。该合成策略依赖于一种前所未有的硅辅助铜酸盐对氨基甲酸酯的S2'-顺式取代，以在CD - 反式氢化茚核心的稠环连接处构建具有挑战性的关键季甲基。其他关键转化包括用CuH对α,β,γ,δ - 不饱和酯进行催化不对称还原，以在C20处生成天然甾体构型，以及进行Pauson - Khand环化以形成CD环骨架。该策略能够合成用于结构 - 功能研究和药物开发的新型类似物。
