Next Article in Journal
New Short Strategy for the Synthesis of the Dibenz[b,f]oxepin Scaffold
Next Article in Special Issue
Fluorescent Probes for Nucleic Acid Visualization in Fixed and Live Cells
Previous Article in Journal
G-Quadruplexes as Sensing Probes
Previous Article in Special Issue
General Approach for Introduction of Various Chemical Labels in Specific RNA Locations Based on Insertion of Amino Linkers
Molecules 2013, 18(12), 14780-14796; doi:10.3390/molecules181214780
Article

Novel Method of Synthesis of 5''-Phosphate 2'-O-ribosyl-ribonucleosides and Their 3'-Phosphoramidites

 and *
Received: 27 September 2013; in revised form: 23 November 2013 / Accepted: 25 November 2013 / Published: 29 November 2013
(This article belongs to the Special Issue Synthesis of Nucleosides, Nucleotides and Their Derivatives)
Download PDF [345 KB, uploaded 18 June 2014]
Abstract: Synthesis of 5''-phosphate 2'-O-ribosylribonucleosides [Nr(p)] of four common ribonucleosides, and 3'-phosphoramidites of 5''-phosphate 2'-O-ribosyladenosine and 2'-O-ribosylguanosine using the H-phosphonate chemistry is described. An additional ring protected by benzoyl groups was incorporated into the main ribosyl ring in the reaction with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose in the presence of SnCl4. The obtained 2'-O-ribosylribonucleosides (Nr) were applied in the subsequent transformations with selective deprotection. Ethanolamine was applied as a very convenient reagent for selective removal of benzoyl groups. Additionally, the tetraisopropyldisiloxane-1,3-diyl (TIPDSi) group was found to be stable under these deprotection conditions. Thus, the selectively deprotected 5''-hydroxyl group of Nr was transformed into an H-phosphonate monoester which was found to be stable under the following conditions: the removal of the TIPDSi group with triethylammonium fluoride and the dimethoxytritylation of the 5''-hydroxyl function. The 5''-H-phosphonate of Nr precursors was easily transformed to the corresponding dicyanoethyl 5''-O-phosphotriesters before phosphitylation, which gave 3'-phosphoramidite units of Nr(p) in high yield. The derived phosphoramidite units were used in an automated oligonucleotide synthesizer to produce dimer Ar(p)T via the phosphoramidite approach. The obtained products were fully deprotected under standard deprotection conditions giving dimers with a 5''-phosphate monoester function. Application of an alkaline phosphatase to prove the presence of an additional phosphate group was described.
Keywords: 2'-O-ribosylribonucleosides; ribosylation; methionine tRNA; initiator tRNA; H-phosphonate; phosphoramidite; nucleosides; nucleotides 2'-O-ribosylribonucleosides; ribosylation; methionine tRNA; initiator tRNA; H-phosphonate; phosphoramidite; nucleosides; nucleotides
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Chmielewski, M.K.; Markiewicz, W.T. Novel Method of Synthesis of 5''-Phosphate 2'-O-ribosyl-ribonucleosides and Their 3'-Phosphoramidites. Molecules 2013, 18, 14780-14796.

AMA Style

Chmielewski MK, Markiewicz WT. Novel Method of Synthesis of 5''-Phosphate 2'-O-ribosyl-ribonucleosides and Their 3'-Phosphoramidites. Molecules. 2013; 18(12):14780-14796.

Chicago/Turabian Style

Chmielewski, Marcin K.; Markiewicz, Wojciech T. 2013. "Novel Method of Synthesis of 5''-Phosphate 2'-O-ribosyl-ribonucleosides and Their 3'-Phosphoramidites." Molecules 18, no. 12: 14780-14796.


Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert