Bioinspired Total Synthesis of Myltayloriones A‐B and Mylnudones A–D

Z Zong‐Xu Gao (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China) X Xiao‐Xue Chen (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China) Y Yue‐Qing Zhang (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China) J Jing Fan P Pei‐Lin Wu (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China) L Ling‐Fei Hu (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China) C Chenyingchun Su Z Zhang‐Qin Xue (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China) M Ming‐Zhu Zhu (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China) P Pei‐Hong Fan (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China) J Jiao‐Zhen Zhang (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China) Y Yan Zong (Department of Biomedical Engineering, College of Future Technology) Z Ze‐Jun Xu (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China) H Hong‐Xiang Lou (State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China)

Abstract

ABSTRACT Herein, we report the first asymmetric synthesis of the dimeric sesquiterpenoid myltayloriones A and B. The synthesis features a stereodivergent Echavarren Au‐catalyzed reaction that enables the synthesis of two subunits from a common dienyne precursor, followed by an endo ‐Diels–Alder heterodimerization. Additional key transformations include a ligand‐controlled Pd‐catalyzed reductive hydrogenolysis for C1 isomerization, and a metal‐catalyzed hydrogen atom transfer (MHAT)‐initiated Baran–Giese cyclization to forge a highly congested penta‐substituted cyclopropane. The selectivity of Pd‐catalyzed hydrogenolysis originates from two different oxidative addition pathways, as further elucidated by density functional theory (DFT) calculations. This synthetic work has enabled further investigation of the potent growth differentiation factor 15 (GDF15) inhibitory and insect antifeedant activity exhibited by myltaylorione A. Furthermore, the developed strategy enabled the concise synthesis of mylnudones A–D and revised the structures of mylnudones A and B.

Article Details

Volume / Issue Vol. 1, Issue 1
Published July 21, 2026
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (14)

Z

Zong‐Xu Gao

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China

X

Xiao‐Xue Chen

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China

Y

Yue‐Qing Zhang

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China

J

Jing Fan

P

Pei‐Lin Wu

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China

L

Ling‐Fei Hu

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China

C

Chenyingchun Su

Z

Zhang‐Qin Xue

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China

M

Ming‐Zhu Zhu

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China

P

Pei‐Hong Fan

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China

J

Jiao‐Zhen Zhang

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China

Y

Yan Zong

Department of Biomedical Engineering, College of Future Technology

Z

Ze‐Jun Xu

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China

H

Hong‐Xiang Lou

State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Key Laboratory of Chemical Biology (Ministry of Education) Shandong Basic Science Special Academic Zone (Pharmacy) Shandong University Jinan P. R. China