Solution‐Phase Synthesis of Branched Oligonucleotides with up to 32 Nucleotides and the Reversible Formation of Materials

A linear solution‐phase synthesis of branched oligonucleotides with adamantane as core has been developed. The method uses conventional phosphoramidites only, achieves chain assembly without chromatography of intermediates, and overcomes the low reactivity of adamantane‐1,3,5,7‐tetraol as core. The assembly of four‐arm hybrids with up to 32 nucleotides total was performed, with monodisperse products of up to 10 kDa in size. Overall yields of 20 % over 19 steps (hexamer arms) and 11 % over 25 steps (octamer arms) of HPLC‐purified compounds were obtained. The adamantane‐based hybrids show more DNA‐dominated assembly properties than their analogues with larger lipophilic cores. Reversible formation of macroscopic amounts of materials through hybridization was achieved, both for self‐complementary systems and two‐hybrid systems with two non‐self‐complementary DNA sequences. A protocol for the solution‐phase synthesis of branched oligodeoxynucleotides was developed that can be scaled up readily and that provides products with the ability to form materials through base pairing.