Synthesis of tacrine- and coumarin-isocryptolepine hybrids as potential dual binding site acetylcholinesterase inhibitors

Abstract

This project presents the synthesis of tacrine and coumarin scaffolds armed with an alkyl-chain of varying length with an azido functionality and isocryptolepine scaffold armed with a terminal alkyne.

The synthesis of these compounds lead to the successful synthesis of the potential dual binding site acetylcholinesterase inhibitors, a tacrine-cryptolepine hybrid with a 3 carbon-linker and a coumarin-isocryptolepine hybrid with a 4 carbon-linker assembled via copper-catalyzed azidealkyne cycloaddition (CuAAC). The attempted synthesis of the same hybrids with different linker-length (6 and 8) were not successful.