Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds

Scheme 5

Synthesis of imidazole polyamide derivatives. Reagents and conditions: i (CH₃)₄N⁺ NO₃⁻, TFAA, CHCl₃, 0°C-rt, 21 (59%), and 22 (24%). ii 1 M NaOH aq./EtOH/pyridine, rt; Dowex 50WX8 (H⁺-form), 23 (quant.); 26 (quant.). iii H₂, 10% Pd/C, 1 : 1 AcOEt/EtOH, rt, 24 (quant.). iv (Boc)₂O, DMF, rt, 25 (quant.); (v) DCI, HOBt, DIEA, DMF, rt, 27 (88%). vi AcCl, EtOH/CHCl₃, rt-40°C. vii 23, EDCI, DMAP, DMF, rt, 28 (84%). viii 9, 10, or 11, DCI, HOBt, DIEA, DMF, rt, 29 (50%); 30 (33%); 31 (71%). Compound 20 was prepared according to the procedure described by Baird and Dervan [30].