美国莱斯大学Renata, Hans团队报道了十种壳梭菌素二萜类化合物的模组化酶合成。相关研究成果发表在2024年5月6日出版的《自然—化学》。

壳梭菌素二萜类化合物具有有趣的生物活性，包括作为14-3-3蛋白质-蛋白质相互作用的调节剂的能力。然而，它们天生的结构复杂性和多样化的氧化模式给合成带来了巨大的挑战。

该文中，研究人员开发了一种结合了从头骨骼构建和后期混合C–H氧化的模块化化学酶方法，以实现8-13个步骤合成10种复杂的壳梭菌素。聚合片段偶联策略能够快速获得一种关键的三环中间体，该中间体经过化学和酶促C–H氧化以模块化制备五个氧化的家族成员。研究人员还构思了一种互补的仿生骨骼重塑策略，以综合获得五种具有不寻常桥头堡双键的重排壳梭菌素。

该项工作可能有助于未来对壳梭菌素的生物活性进行研究，并启发实施类似的混合策略，为其他天然产品支架提供家族级合成解决方案。

附：英文原文

Title: Modular chemoenzymatic synthesis of ten fusicoccane diterpenoids

Author: Jiang, Yanlong, Renata, Hans

Issue&Volume: 2024-05-06

Abstract: Fusicoccane diterpenoids display intriguing biological activities, including the ability to act as modulators of 14-3-3 protein–protein interactions. However, their innate structural complexity and diverse oxygenation patterns present enormous synthetic challenges. Here we develop a modular chemoenzymatic approach that combines de novo skeletal construction and late-stage hybrid C–H oxidations to achieve the synthesis of ten complex fusicoccanes in 8–13 steps each. A convergent fragment coupling strategy allowed rapid access to a key tricyclic intermediate, which was subjected to chemical and enzymatic C–H oxidations to modularly prepare five oxidized family members. We also conceived a complementary biomimetic skeletal remodelling strategy to synthetically access five rearranged fusicoccanes with unusual bridgehead double bonds. This work may facilitate future investigation into the biological activities of the fusicoccanes and also inspire the implementation of similar hybrid strategies to provide family-level synthetic solutions to other natural product scaffolds.

DOI: 10.1038/s41557-024-01533-w

Source: https://www.nature.com/articles/s41557-024-01533-w