A two-step sulfurization for efficient solution-phase synthesis of phosphorothioate oligonucleotides |
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| Authors: | Amar BT Ghisaidoobe Howard I Duynstee Herman S Overkleeft Gijs A van der Marel |
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| Institution: | a Leiden Institute of Chemistry, Gorlaeus Laboratories, PO Box 2502, 2300 RA, Leiden, The Netherlands
b Diosynth B.V., PO Box 20, 5340 BH, Oss, The Netherlands |
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| Abstract: | A solution-phase approach for the synthesis of phosphorothioate oligonucleotides that circumvents the use of chromatographic purifications of protected phosphorothioate intermediates was developed. Implementation of a two-step sulfurization protocol in the phosphoramidite method allows efficient isolation of the intermediate phosphorothioates by extractions. The viability of this approach is demonstrated by the synthesis of a hexameric phosphorothioate oligonucleotide fragment. |
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