Design, synthesis, and evaluation of trisubstituted bicyclo[2.2.2]oct-2-enes as non-classical isosteres of trisubstituted benzenes

2026/01/01 by Chih‐Wei Hsu, Wei-Qi Liu, Fang-Jie Shih +6 · 1 voice
Chemistry · #Organic Chemistry Cycloaddition Reactions #Synthetic Organic Chemistry Methods #Cyclization and Aryne Chemistry

paper · doi:10.1039/d6ob00798h

openalex publication_date 2026/01/01 · openalex created_date 2026/06/12 · openalex updated_date 2026/07/09

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.

Citations

• Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density
• Density-functional thermochemistry. III. The role of exact exchange
• A generally applicable atomic-charge dependent London dispersion correction

Discussions

• Check out this paper by Sung-Fang Chen, Woo-Jin Yoo et al. from National Taiwan University in our latest issue on the synthesis of trisubstituted bicyclo[2.2.2]oct-2-enes as non-classical isosteres of [bsky, 0 points, 0 comments]