Diversity-Oriented Synthesis of Highly Fluorescent Fused-isoquinolines for Specific Subcellular Localization.

A multicomponent Diversity-Oriented Synthesis of new highly emissive tetracyclic isoquinolines that target specific organelles is described. The title compounds were prepared via a three-step protocol starting with an Ugi four-component reaction, followed by either an intramolecular alkyne hydro-arylation and subsequent alkene isomerization, or through a Pomeranz–Fritsch type cyclization with a final intramolecular Heck reaction. Subcellular localization studies of these compounds using green-channel confocal microscopy revealed remarkable and distinctive distribution patterns in live cells, showing an unprecedent high selectivity and imaging contrast. The differentiated organelle visualization -including localizers for mitochondria, lysosomes, Golgi apparatus, endoplasmic reticulum and plasma membrane- was achieved by varying the nature of the tetracyclic system and substituent pattern, changing the original four-component set in the starting Ugi reaction.