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-nitrophenylsulfonyl)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.
Zhang
Zhibo
Z
Department of Chemistry, Turku University, FIN-20014 Turku.
Mikkola
Satu
S
Lönnberg
Harri
H
D003300:Copper / Q000737:chemistry; D009690:Nucleic Acid Conformation; D011725:Pyridines / Q000737:chemistry*; D012315:RNA Caps / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
D011725:Pyridines; D012315:RNA Caps; D003300:Copper; D015032:Zinc