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Polyazacyclophanes Incorporating Two Pyridine Units and a Heteroaromatic Pendant Group as Potential Cleaving Agents of mRNA 5′‐ cap Structure
Author(s) -
Zhang Zhibo,
Mikkola Satu,
Lönnberg Harri
Publication year - 2005
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200590081
Subject(s) - chemistry , pyridine , alkylation , cleave , anhydrous , carbamate , ring (chemistry) , stereochemistry , methyl group , protecting group , amino acid , intermolecular force , medicinal chemistry , group (periodic table) , organic chemistry , enzyme , molecule , catalysis , biochemistry , alkyl
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.