Effect of microwave irradiation on phosphoramidite couplings on controlled pore glass

The chain extension step in the synthesis of DNA oligomers on controlled pore glass was shown to be higher yielding when the reaction mixture is irradiated with microwaves. Both a commercial thymidine 3'-phosphoramidite building block and a 3'-phosphoramidite of protected 1'-aminomethylthymidine were coupled using dilute solutions that give only partial conversion. In either case, higher coupling yields were observed when microwaves were used. The results of our exploratory experiments suggest that microwave-assisted DNA syntheses might require fewer equivalents of phosphoramidites and/or shorter coupling times than those performed at room temperature.