Nucleotide synthesis, liquid-phase

Turowski, M., Kaliszan, R., Lullmann, C., Genieser, H. G., and Jastorff, B., New stationary phases for the high performance liquid chromatographic separation of nucleosides and cyclic nucleotides. Synthesis and chemometric analysis of retention data, /. Chromatogr. A, 728, 201-211, 1996. 

Conventional liquid phase synthesis suffers from the limitation that each product or intermediate has to be separated from the other components of the reaction mixture. An elegant answer to this problem is to use a solid phase synthesis (SPS) approach. In such an approach the compounds are synthesized on a solid support and simple washing steps replace the laborious work up and isolation procedures. At the end of the synthesis the product is released from the solid support. The SPS of oligomers of amino acids or nucleotides is well estabilished and task chemists are facing now is the development of SPS routes for small organic molecules. 

Brandstetter F, Schott H, Bayer E, Liquid phase synthesis of nucleotides, Tetrahedron Lett., 2997-3000, 1973. 

Comparable to peptide synthesis, the liquid-phase synthesis of oligonucleotides is based on the sequential repetition of reaction steps, thus adding one monomeric nucleotide to the other (Scheme 4). 

The preparation and availability of suitable soluble polymer supports are basic requirements for the successful application of liquid-phase synthesis of peptides and nucleotides. Many parameters have to be considered when designing appropriate supports and the route of synthesis and the target product of synthesis must also be considered. Liquid-phase synthesis requires optimum solubility properties of the polymer supports and therefore the adaption of the functional capacity to the solubilizing power of the polymer backbone and side-chains is the determining step before synthesis. The main factors of evaluation are the solubility characteristics of the polypeptide or oligonucleotide to be synthesized. 

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