Affiliation:
1. Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and Engineering Southwest Jiaotong University Chengdu 610031 P. R. China
2. College of Chemistry Leshan Normal University Leshan 614004 P. R. China
3. Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University Chengdu 610041 P. R. China
Abstract
Abstract(−)‐Adenophorone (1), a caged polycyclic sesquiterpene featuring an unprecedented tricyclo[4.3.1.05,9]decane skeleton, was isolated from Eupatorium adenopharum Spreng. The structure of 1 was unambiguously established by a combination of spectroscopic analysis, X‐ray crystallography, and bioinspired total synthesis. Key synthetic features include a sequential Reformatsky/oxidation/regio‐ and stereoselective hydrogenation, and subsequent merged MBH–Tsuji–Trost cyclization. The concise synthetic sequence efficiently constructs the bicyclic skeleton of cadinene sesquiterpene (+)‐euptox A (2) in 8 steps from commercially available monoterpene (−)‐carvone (6), with outstanding performance on diastereocontrol. The bioinspired synthesis of 1 was achieved from 2, a plausible biogenetic precursor, via transannular Michael addition. This work provides experimental evidence of our proposed biosynthetic hypothesis of 1. Additionally, compound 1 showed potent neuroprotective activity in H2O2‐treated SH‐SY5Y and PC12 cells.
Funder
National Natural Science Foundation of China