Synthesis of Short Oligodeoxyribonucleotides by Phosphotriester Chemistry on a Precipitative Tetrapodal Support

Abstract Short oligodeoxyribonucleotides have been assembled from appropriately protected nucleoside 3′‐(benzotriazol‐1‐yl 2‐chlorophenyl phosphate) derivatives on hundred‐milligram scales on a soluble tetrakis‐ O ‐(4‐azidomethylphenyl)pentaerythritol support bearing four 3′‐ O ‐(4‐pentynoyl)thymidines. Small‐molecule reagents and waste were removed by two precipitations of the support‐bound growing oligonucleotides with methanol, the first after removal of the 5′‐protecting group and the second after coupling. The building blocks were obtained by one‐step phosphorylation of commercially available protected nucleosides with bis(benzotriazol‐1‐yl) 2‐chlorophenyl phosphate. Removal of the phosphate protecting groups from the completed chain with ( E )‐2‐nitrobenzaldoxime followed by conventional ammonolysis allowed precipitation of the oligonucleotide as the sodium salt with ethanol.