北京大学徐正仁团队报道了二萜类天然产物环烷家族的化学酶法合成。相关研究成果发表在2024年11月27日出版的《德国应用化学》。

报道了环丙烷家族和相关二萜的三阶段化学酶合成。具有6/5/5/5-折叠四环环环丙烷骨架的脱氧内生内生醇，首先由携带相应萜环化酶PchDS的工程大肠杆菌宿主产生。分别通过直接氧化还原操作、直接C-H活化和酶羟基化对环烷骨架的环A、B和D进行后期官能化，合成了10种环烷二萜。

骨架多样化是通过利用化学或酶法产生的，环烷阳离子的选择性1,2-烷基迁移来实现的。三种与环戊烷相关的骨架，包括螺紫烯的螺环5/5/5/5-四环骨架、phomopsene的角形5/6/5/5-5-环状系统和amycolatene的新线性5/6/5/5-四环系统，要么是通过环戊烷骨架的化学骨架转化产生的，要么是通过基因组挖掘发现的萜烯环化酶产生的。

附：英文原文

Title: Chemoenzymatic Synthesis of the Cyclopiane Family of Diterpenoid Natural Products

Author: Zhengren Xu, Tao Wang, Jiasheng Zou, Kaibiao Wang, Yuanning Liu, Shouqi Zhang, Yao Kong

Issue&Volume: 2024-11-27

Abstract: A three-stage chemoenzymatic synthesis of the cyclopiane family and related diterpenes is reported. Deoxyconidiogenol with a 6/5/5/5-fused tetracyclic cyclopiane skeleton was first produced by an engineered E. coli host harboring the corresponding terpene cyclase PchDS. Ten cyclopiane diterpenes were synthesized by late-stage functionalization of rings A, B and D of the cyclopiane skeleton through direct redox operations, directed C-H activation, and enzymatic hydroxylation, respectively. Skeletal diversification was achieved by taking advantage of the selective 1,2-alkyl migration of a cyclopiane cation generated chemically or enzymatically. Three cyclopiane-related skeletons, including the spiro 5/5/5/5-tetracyclic skeleton of spiroviolene, the angular 5/6/5/5-fused ring system of phomopsene, and the new linear 5/6/5/5-fused tetracyclic ring system of amycolatene, were produced either by chemical skeletal transformation from the cyclopiane skeleton, or by terpene cyclases discovered by genome mining.

DOI: 10.1002/anie.202419092

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202419092