Aude Mary

Potent acetylcholinesterase inhibitors: design, synthesis, and structure–Activity relationships of bis-interacting ligands in the galanthamine series

New galanthamine derivatives, especially bis-interacting ligands 3-5 and 7-9 were prepared in order to interact with the catalytic and the peripheral sites of acetylcholinesterase (AChE). The synthesis, the anticholinesterase activities, and the structure-activity relationships of bis-interacting ligands are reported. Compounds 4d-e were found to be more potent than galanthamine and tacrine in inhibiting AChE.

Selective N-demethylation of galanthamine to norgalanthamine via a non classical Polonovski reaction

Abstract The previously unknown N-demethylation of galanthamine 1 to norgalanthamine 3 was selectively accomplished by a non classical Polonovski reaction using iron salts. This transformation constitutes the first example of the application of the Polonovski reaction to an N-oxide of a seven membered cyclic amine. Norgalanthamine is a valuable intermediate in new galanthamine derivatives synthesis.

UNEXPECTED HYDROXYLATION OF GALANTHAMINE DURING THE COURSE OF A POLONOVSKI-POTIER REACTION

Abstract Galanthamine N-oxide 2 undergoes a Polonovski-Potier reaction to give the iminium salt 5 and the unexpected 8-hydroxygalanthamine 3. An intramolecular oxygen transfer is proposed to explain hydroxylation of the aromatic nucleus.