abstract |
New methods of synthesizing oligonucleotides are disclosed. The methods result in improved yields by reducing or eliminating depurination that often occurs during detritylation. The method comprises detritylating DMT-blocked oligonucleotides with dichloroacetic acid in combination with a lower alcohol (e.g., methanol or ethanol) or 1H-pyrrole. The method is advantageously used to synthesize oligonucleotides up to about 150 monomers long. |