School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, P. R. China.
Org Biomol Chem. 2021 Mar 28;19(12):2767-2772. doi: 10.1039/d0ob02398a. Epub 2021 Mar 10.
Lycorine-type alkaloids are privileged structures in drug development due to their attractive biological activities. In this paper, the carbonyl on the C ring was proved to have played a critical role in stereoselectivity during the synthesis process, and the galanthan skeleton with a cis-B/C ring is more thermodynamically stable in its presence. Furthermore, the total synthesis of (±)-β-lycorane was successfully completed by employing the Michael addition reaction to construct the galanthan skeleton with a trans-B/C ring. This system might be applied to other structural types with similar stereochemistry setting.
石蒜科生物碱因其具有吸引人的生物活性而成为药物开发中的优势结构。在本文中，证明 C 环上的羰基在合成过程中对立体选择性起着关键作用，并且在其存在下具有顺式-B/C 环的加兰他敏骨架在热力学上更稳定。此外，通过迈克尔加成反应构建具有反式-B/C 环的加兰他敏骨架，成功地完成了(±)-β-石蒜碱的全合成。该体系可能适用于具有类似立体化学环境的其他结构类型。
