Qiao Jin-Bao, Meng Long, Pei Jia-Yi, Shao Hui, Zhao Yu-Ming
Key Laboratory of Applied Surface and Colloid Chemistry & School of Chemistry and Chemical Engineering, Shaanxi Normal University, 620 West Chang'an Ave, Xi'an, 710119, China.
Angew Chem Int Ed Engl. 2025 Jan 27;64(5):e202417647. doi: 10.1002/anie.202417647. Epub 2024 Nov 6.
Ryanodane diterpenes are structurally complex natural products that are well-known for their high degree of oxidation and the challenges associated with synthesizing them within the terpene class. Herein, we present a two-stage synthetic strategy that draws inspiration from the broad biosynthesis of terpenes, allowing us to achieve the first chemical synthesis of garajonone, a ryanodane diterpenoid that occurs naturally at low abundance, as well as its epimer, 3-epi-garajonone. The key to this success lies in the rapid construction of the carbon framework of the target molecule by employing an early-stage palladium-catalyzed Heck/carbonylative esterification cascade annulation, followed by successive late-stage selective redox manipulation to establish the desired oxidation state of the molecule. This research not only showcases the synthesis of garajonone and its epimer but also provides a platform for the chemical synthesis of other members and analogs of this complex diterpenoid family.
瑞诺烷二萜是结构复杂的天然产物，以其高度的氧化程度以及在萜类化合物中合成它们所面临的挑战而闻名。在此，我们提出了一种两阶段合成策略，该策略从萜类化合物广泛的生物合成中汲取灵感，使我们能够首次化学合成低丰度天然存在的瑞诺烷二萜类化合物加拉霍酮及其差向异构体3-表加拉霍酮。这一成功的关键在于通过早期钯催化的 Heck/羰基化酯化级联环化反应快速构建目标分子的碳骨架，随后在后期进行连续的选择性氧化还原操作以建立分子所需的氧化态。这项研究不仅展示了加拉霍酮及其差向异构体的合成，还为该复杂二萜类化合物家族的其他成员和类似物的化学合成提供了一个平台。
