Preparation of zwitterionic ribonucleoside phosphoramidites for solid-phase siRNA synthesis
Romualdas Smicius1, Joachim W Engels
1Institut für Organische Chemie und Chemische Biologie, Johann Wolfgang Goethe-Universität, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany.
The Journal of Organic Chemistry
|June 5, 2008
Summary
Researchers developed a fast synthesis for 2'-aminoethyl RNA building blocks. These modified oligoribonucleotides enhance antisense strategies by improving drug properties and neutralizing the RNA backbone.
Area of Science:
- Biochemistry
- Organic Chemistry
- Medicinal Chemistry
Background:
- RNA oligomers with 2 -O-modified nucleosides are valuable tools for antisense strategies like RNA interference (RNAi).
- The 2 -O-alkyl modification with amino functionality is particularly important for neutralizing the negatively charged phosphate backbone.
- This neutralization improves the physicochemical and pharmaceutical properties of antisense agents.
Purpose of the Study:
- To develop a concise and efficient synthesis for phosphoramidites of all four 2 -aminoethyl-modified natural ribonucleosides.
- To facilitate the creation of advanced antisense agents with enhanced properties.
Main Methods:
- A single-step alkylation strategy was employed to introduce the aminoethyl group.
- Synthesis focused on creating phosphoramidites for guanosine, adenosine, cytidine, and uridine derivatives.
Main Results:
- A short, convenient, and straightforward synthesis was achieved for the target phosphoramidites.
- The method allows for the preparation of all four natural ribonucleoside derivatives modified with a 2 -aminoethyl group.
Conclusions:
- The developed synthesis provides essential building blocks for novel antisense agents.
- These modified nucleosides offer a promising route to improved RNA-based therapeutics.
