Division of Organic Chemistry , CSIR-National Chemical Laboratory , Pune 411008 , India.
Academy of Scientific and Innovative Research (AcSIR) , New Delhi 110025 , India.
Org Lett. 2019 Nov 15;21(22):9089-9093. doi: 10.1021/acs.orglett.9b03477. Epub 2019 Oct 30.
The enantioselective formal total synthesis of (-)-quinagolide has been accomplished in a linear sequence of 8 purification steps from pyridine. The key steps are (a) organocatalyzed Diels-Alder reaction for fixing all three stereocenters on piperidine ring; (b) protecting group enabled deoxygenation of isoquinuclidine skeleton under Birch reduction condition; (c) Lewis acid (TiCl) catalyzed intramolecular Friedel-Crafts cyclization of dicarboxylic acid; and (d) one-pot diastereoselective ketone reduction-intramolecular cyclization to form oxazolidinone which enables -geometry installation. During the course of the synthesis, an interesting reductive cleavage of the C-N bond in the electron-deficient isoquinuclidine skeleton under the Birch reduction conditions has been observed. This is the first synthetic effort to access the core skeleton of (-)-quinagolide.
（-）-喹那高利德的对映选择性形式全合成已经从吡啶通过 8 步纯化步骤以线性序列完成。关键步骤是：(a) 有机催化 Diels-Alder 反应，固定哌啶环上的所有三个立体中心；(b) 在 Birch 还原条件下，通过保护基实现异喹诺啉骨架的脱氧；(c) Lewis 酸（TiCl）催化的二酸的分子内 Friedel-Crafts 环化；(d) 一锅法非对映选择性酮还原-分子内环化形成噁唑烷酮，从而实现 - 几何结构的安装。在合成过程中，在 Birch 还原条件下，缺电子异喹诺啉骨架中的 C-N 键发生了有趣的还原裂解。这是首次尝试合成（-）-喹那高利德的核心骨架。
