Festphasensynthese von oligonucleotiden, 11. Verwendung eines neuartigen hydrophilen perlpolymerisats als träger

New hydrophilic swellable and lowly crosslinked bead copolymers consisting of dimethylaminocarbonylethylene or -propylene and alkoxycarbonylethylene or -propylene repeating units were prepared starting from activated esters of acrylic acid ( 8a–10a ) or methacrylic esters ( 8b–10b ) and N,N-dimethylacrylamide ( 12a ). This “hydrophylic Merrifield carriers” were applied for polymer-supported oligodeoxynucleotide syntheses. They were found to be swellable in a wide range of solvents. The first deoxynucleoside was attached to the carrier via its 5′-hydroxyl group by an ester bond. The cleavage of the bond between carrier and oligonucleotide was performed with aqueous sodium hydroxide under conditions which do not attack the N-protecting groups attached to the oligonucleotide chain. The acid labile 1-ethoxyethyl group was used as 3′-protecting group for the phosphate component (N-protected deoxynucleoside-5′-phosphate). Some suitable protected deoxynucleosides were synthesized for anchoring and deoxynucleoside-5′-phosphates for chain elongation. In a condensation reaction according to the diester method, a dinucleoside monophosphate ( 7 ) was prepared and, as a consequence of the flexibility of the polymeric backbone, the synthesis of longer oligonucleotides should be feasible. The alkali labile anchoring of the oligonucleotides to the carrier can allow to avoid wrong sequences by simple acylation of the non-reacted 3′-OH groups with acetic anhydride after each condensation step.