Design, synthesis, and evaluation of trisubstituted bicyclo[2.2.2]oct-2-enes as non-classical isosteres of trisubstituted benzenes
Journal
Organic and Biomolecular Chemistry
Journal Volume
24
Journal Issue
26
Start Page
5488
End Page
5493
ISSN
1477-0520
1477-0539
Date Issued
2026
Author(s)
Hsu, Chih-Wei
Liu, Wei-Qi
Shih, Fang-Jie
Jheng, Yong-Jin
Chou, Chih-Hui
Wang, Yu-Meng
Chen, Sung-Fang
Abstract
The limited availability of polycyclic hydrocarbon scaffolds that accurately mimic the torsional angles of polysubstituted benzenes poses a challenge in bioisostere design. To address this issue, we propose bicyclo[2.2.2]oct-2-enes as readily accessible structural isosteres of polysubstituted benzenes. To evaluate this hypothesis, a series of fungicide and antineoplastic analogs that incorporate the bicyclo[2.2.2]oct-2-ene core were synthesized. These patent-free compounds underwent structural characterization and biological validation, which confirmed their potential as isosteric replacements for the benzene ring.
Publisher
Royal Society of Chemistry (RSC)
Type
journal article