Synthesis of a D‑Ring Isomer of Galanthamine via a Radical-Based Smiles Rearrangement Reaction

Abstract

The 1,9-ethanoiminomethano-bridged tetra­hydro­di­benzo­[<i>b</i>,<i>d</i>]-furan <b>2</b>, a non-natural isomer of the alkaloid (−)-galanthamine (<b>1</b>) varying in the manner in which the D-ring is annulated to the ABC-core, has been prepared in racemic form. The synthetic sequence starts with the cyclopropane <b>3</b> and involves intramolecular Heck alkenylation and radical-based Smiles rearrangement reactions as key steps. Unlike natural product <b>1</b>, but as predicted by docking studies, compound <b>2</b> is not a potent inhibitor of acetylcholine esterase