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 in20121,2. From the chemical point of view, it is a benzo[ghi]perylen-diimmide presenting a piperidingroup on the minor axis of the molecule directly linked to the bay area of the perylen core and threeethyl-piperidin chains, one linked to the aromatic area of the core and the other two linked to themajor axis by a diimmidic bond.This compound has proved to be able to inhibit the growth of tumor cells through a double mechanismi.e. the inhibition of telomerase at high doses and, at minor concentrations, the induction of apopotosisof the tumor cells by rapidly triggering extensive DNA damage of telomeres, associated with thedelocalization of telomeric protein protection of telomeres 1 (POT1)1. EMICORON has also showedto be effective in inhibiting the colon-rectal tumors in rats3 both as single compound both in a synergiceffect with other conventional antitumor drugs3,4.In this work, we report the modification of two synthetic steps in respect with the usual ones in orderto obtain a final higher yield for this compound. In particular, for what concerns the first one, wemodified the times and the work up of the reaction whereas, for what concerns the second one, wecompletely modified the reaction conditions. We eliminated dioxane and hydroquinone and the newreaction occurred in shorter times, at lower temperatures and piperidine was used as reagent andsolvent contemporaneously (Figure). With the modifications made to these two reaction steps, theglobal 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 tocarry out further preclinical studies.