New developments in the synthesis of EMICORON, a promising inhibitor of telomerase

EMICORON is a compoud which was synthesized for the first time in our own laboratory in 20121,2. From the chemical point of view, it is a benzo[ghi]perylen-diimmide presenting a piperidin group on the minor axis of the molecule directly linked to the bay area of the perylen core and three ethyl-piperidin chains, one linked to the aromatic area of the core and the other two linked to the major axis by a diimmidic bond. This compound has proved to be able to inhibit the growth of tumor cells through a double mechanism i.e. the inhibition of telomerase at high doses and, at minor concentrations, the induction of apopotosis of the tumor cells by rapidly triggering extensive DNA damage of telomeres, associated with the delocalization of telomeric protein protection of telomeres 1 (POT1)1. EMICORON has also showed to be effective in inhibiting the colon-rectal tumors in rats3 both as single compound both in a synergic effect with other conventional antitumor drugs3,4. In this work, we report the modification of two synthetic steps in respect with the usual ones in order to obtain a final higher yield for this compound. In particular, for what concerns the first one, we modified the times and the work up of the reaction whereas, for what concerns the second one, we completely modified the reaction conditions. We eliminated dioxane and hydroquinone and the new reaction occurred in shorter times, at lower temperatures and piperidine was used as reagent and solvent contemporaneously (Figure). With the modifications made to these two reaction steps, the global yield of the process has increased passing from 28% (original procedure)1 to 40%. Thus, this new procedure may be more suitable in order to get larger amounts of EMICORON to carry out further preclinical studies.