Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1988 Oct 11;16(19):9285–9298. doi: 10.1093/nar/16.19.9285

Studies on the t-butyldimethylsilyl group as 2'-O-protection in oligoribonucleotide synthesis via the H-phosphonate approach.

J Stawinski 1, R Strömberg 1, M Thelin 1, E Westman 1
PMCID: PMC338706  PMID: 3174451

Abstract

Two model compounds, 1 and 2, have been studied to test the stability of the t-butyldimethylsilyl (t-BDMSi) group towards conditions used during chemical synthesis of RNA fragments by the H-phosphonate approach. When 1 was treated with anhydrous acid for 16 h both the H-phosphonate diester and the t-BDMSi group remained intact. Removal of the t-BDMSi group from 2 with 1.0 M tetrabutylammonium fluoride (TBAF .3H2O) in THF was complete within 4 h and neither concomitant cleavage nor migration of the phosphodiester linkage could be detected even after 24 h. The dimer 2 was not completely stable towards concentrated aqueous ammonia and both loss of the t-BDMSi group and concomitant cleavage of the phosphodiester linkage occurred upon prolonged treatment. These reactions were substantialy suppressed in ethanol containing ammonia solutions, however to alleviate this problem during oligoribonucleotide synthesis, more labile protecting groups for heterocyclic bases would be desired. In conclusion, these studies indicate that 2'-O-t-BDMSi can be considered as a convenient and safe protecting group, which should secure synthesis of oligoribonucleotides with exclusively 3'-5' internucleotidic linkages.

Full text

PDF
9286

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Froehler B. C., Ng P. G., Matteucci M. D. Synthesis of DNA via deoxynucleoside H-phosphonate intermediates. Nucleic Acids Res. 1986 Jul 11;14(13):5399–5407. doi: 10.1093/nar/14.13.5399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Lindeke B., Ericsson O., Jönsson A., Noren B., Strömberg S., Vangbo B. Biotransformation of terodiline. III. Opposed stereoselectivity in the benzylic and aromatic hydroxylations in rat liver microsomes. Xenobiotica. 1987 Nov;17(11):1269–1278. doi: 10.3109/00498258709047158. [DOI] [PubMed] [Google Scholar]
  3. Schulhof J. C., Molko D., Teoule R. The final deprotection step in oligonucleotide synthesis is reduced to a mild and rapid ammonia treatment by using labile base-protecting groups. Nucleic Acids Res. 1987 Jan 26;15(2):397–416. doi: 10.1093/nar/15.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Strömberg R., Stawinski J. Evaluation of some new condensing reagents for hydrogenphosphonate diester formation. Nucleic Acids Symp Ser. 1987;(18):185–188. [PubMed] [Google Scholar]
  5. Tanaka T., Tamatsukuri S., Ikehara M. Solid phase synthesis of oligoribonucleotides using o-nitrobenzyl protection of 2'-hydroxyl via a phosphite triester approach. Nucleic Acids Res. 1986 Aug 11;14(15):6265–6279. doi: 10.1093/nar/14.15.6265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Tanaka T., Tamatsukuri S., Ikehara M. Solid phase synthesis of oligoribonucleotides using the o-nitrobenzyl group for 2'-hydroxyl protection and H-phosphonate chemistry. Nucleic Acids Res. 1987 Sep 25;15(18):7235–7248. doi: 10.1093/nar/15.18.7235. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES