Synthesis of protected 2′-O-deoxyribonucleotides on a precipitative soluble support: a useful procedure for the preparation of trimer phosphoramidites?

RSC Advances Pub Date: 2016-10-31 DOI: 10.1039/C6RA22316H

Abstract

Tetrakis-O-(4-azidomethylphenyl)pentaerythritol, derivatized with 5′-O-(4,4′-dimethoxytrityl)-3′-O-{4-[2-(but-3-yn-1-ylamino)-2-oxoethoxy]phenoxyacetyl}thymidine, was used as a soluble support to assemble fully protected 2′-O-deoxyribonucleotide trimers by the phosphotriester chemistry. After the coupling and detritylation steps, the support-bound construct was purified by precipitation in MeOH. The trimers (TAT, AGT, TTA, CAT, GCT), in fully protected form, were released by a treatment with dilute methanolic K2CO3 and filtered through a short silica gel column in 65–70% overall yield. Two of the trimers (CAT and GCT), prepared in 0.5 mmol scale, were converted to the corresponding phosphoramidites. The entire procedure for the preparation of trimer phosphoramidites proved straightforward and applicable for the large scale synthesis.

Graphical abstract: Synthesis of protected 2′-O-deoxyribonucleotides on a precipitative soluble support: a useful procedure for the preparation of trimer phosphoramidites
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