Bernhard Küenburg

NEW KILOGRAM-SYNTHESIS OF THE ANTI-ALZHEIMER DRUG (-)-GALANTHAMINE

A concise, scalable synthesis of (−)-galanthamine, a drug being used for the treatment of Alzheimers disease, is described. The yield of the critical phenolic coupling step was optimized to 45–50%. For the reduction of the aryl bromide, air-activated LiAIH4 was used and racemic narwedine was converted to (−)-narwedine by a second order asymmetric transformation.

Enantiomeric resolution of galanthamine and related drugs used in anti-Alzheimer therapy by means of capillary zone electrophoresis employing derivatized cyclodextrin selectors

An analytical assay is presented for the determination of the enantiomeric composition of galanthamine and related synthetic and natural compounds. (-)-Galanthamine is isolated from Galanthus nivalis and is used in this optical pure form in the therapy of Alzheimers disease. Recent efforts for a total synthesis of unichiral (-)-galanthamine is connected with the need for a fast and reliable assay for the determination of the optical purity of the end product, as well as for optimizing and controlling the final steps in total synthesis particularly the asymmetric transformation of narwedine. In this paper the enantiomeric resolution of these compounds is reported employing a capillary electrophoretic system with beta-cyclodextrin derived chiral selectors. With the proposed system a number of galanthamine and narwedine derived analogous compounds could be separated, including 1-bromo- and N-alkyl-substituted compounds.