Synthesis of Deoxyoligonucleotides on an Isotactic Polymer Support

Abstract

An insoluble and noncross-linked polymer of isotactic polystyrene having a p-methoxytrityl group as part of its structure was chosen as a solid polymer support for deoxyribonucleotide synthesis. The p-methoxytrityl functional group was introduced into the isotactic polymer by benzoylation and Grignard reaction. Judging by the NMR spectra, the isotacticity of the polymer remains unaffected after the modifications. Deoxy-nucleosides were linked to the polymer via 5′ ether group. Condensation of the polymer-nucleoside derivative with 3′ protected nucleotides in the presence of mesitylene sulfonyl chloride resulted in 36-63% coupling to the bound nucleoside. Subsequent condensation gave the trinucleoside diphosphate in 25-57% conversion, based on polymer-bound dinucleoside phosphate. The limitation of the polymer support still lies in the low yield of the coupling step, but the value of an isotactic polymer backbone as a “dendritic” center for chain lengthening remains attractive.