Polyazacyclophanes Incorporating Two Pyridine Units and a Heteroaromatic Pendant Group as Potential Cleaving Agents of mRNA 5′‐cap Structure

Four hexaazacyclophanes, 16a-d, incorporating two pyridine units and a (pyridin-2-yl )methyl or (quinolin-2-yl)methyl pendant group at one of the ring N-atoms have been prepared. The key step of the synthesis is an intermolecular cyclization of N,N-bis([6-(tosyloxymethyl)pyridin-2-yl]methyl}-2-nitrobenzenesulfonamide (7) with either tert-butyl bis{2-[(2-nitrophenylsulfonyl)amino]ethyl}carbamate (2a) or tert-butyl bis{3-[(2-nitro-phenylsulfonyl)amino]propyl}carbamate (2b) in the presence of anhydrous Cs 2 CO 3 . Removal of the acid-labile tert-butoxycarbonyl protection then allows attachment of the pendant group by reductive alkylation to the exposed secondary amino group, and deprotection of the remaining aliphatic ring N-atoms completes the synthesis. The ability'of the cyclophanes and their dinuclear Cu 2 - and Zn 2 + complexes to cleave the mRNA cap structure. m 7 G(5')pppG(5') (1). has been studied.