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

The 1,9-ethanoiminomethano-bridged
tetra­hydro­di­benzo­[b,d]-furan 2, a non-natural
isomer of the alkaloid (−)-galanthamine (1) 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 3 and involves intramolecular Heck alkenylation
and radical-based Smiles rearrangement reactions as key steps. Unlike
natural product 1, but as predicted by docking studies,
compound 2 is not a potent inhibitor of acetylcholine
esterase.