Herein, we describe a versatile and efficient total synthesis of 1α,25-dihydroxyvitamin D₃ (calcitriol). The synthetic strategy relies on an unprecedented Si-assisted S_N2′-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.

中文翻译：

---

通过硅辅助的烯丙基取代合成1α，25-二羟基维生素D ₃（骨化三醇）

在这里，我们描述了1α，25-二羟基维生素D ₃（骨化三醇）的通用有效的全合成方法。合成策略依赖于一个前所未有的Si-辅助小号_Ñ 2'-顺由铜酸盐氨基甲酸酯的位移来设定挑战枢轴季甲基在的稠环结CD -反式-hydrindane芯。其他关键转化包括用CuH催化α，β，γ，δ不饱和酯的催化不对称还原，以在C20处生成天然甾体构型，以及进行Pauson-Khand环化反应以形成CD环骨架。这种策略使得能够合成用于结构功能研究和药物开发的新型类似物。