A rapid and convenient synthesis of poly-thymidylic acid by the modified triester approach

Abstract

By using anhydrous triethylamine-pyridine to selectively remove the cyanoethyl group from the fully protected oligo-nucleotide, a substantial improvement has been achieved in yields and the rates of condensation by the modified triester approach from the 5'→3' end. The unreacted oligonucleotide containing the 5'-hydroxy group was removed by treatment with bis (triazolyl)- p -chlorophenyl phosphate after each condensation in situ . These modifications, as exemplified by the synthesis of fully protected T ₁₂ , T ₁₈ , T ₂₄ . and T ₃₈ in 80%, 77%, 70% and 50% yields respectively, should allow the ready synthesis of polynucleotides of even longer chain lengths by purely chemical methods.