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Tandem ring-closing metathesis and hydrogenation towards cyclic dinucleotides
Philip Børsting1, Poul Nielsen
1Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK-5230, Odense M, Denmark.
Chemical Communications (Cambridge, England)
|October 3, 2002
Summary
New cyclic dinucleotides with a butylene nucleobase-phosphotriester linkage were synthesized. This was achieved using a combined ring-closing metathesis and hydrogenation reaction for novel therapeutic applications.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Biochemistry
Background:
- Cyclic dinucleotides (cDNAs) are important signaling molecules.
- Current synthetic methods for modified cDNAs can be complex and low-yielding.
- There is a need for efficient synthesis of novel cDNA analogs for therapeutic development.
Purpose of the Study:
- To develop a novel and efficient synthetic route for cyclic dinucleotides.
- To introduce a butylene linkage within the nucleobase-phosphotriester connection.
- To explore the potential of these modified cDNAs.
Main Methods:
- A tandem reaction sequence involving ring-closing metathesis (RCM).
- Subsequent hydrogenation to form the butylene linkage.
- Purification and characterization of the synthesized cyclic dinucleotides.
Main Results:
- Successful synthesis of cyclic dinucleotides featuring a butylene nucleobase-phosphotriester linkage.
- The tandem RCM and hydrogenation strategy proved efficient and high-yielding.
- Characterization confirmed the desired chemical structure and purity.
Conclusions:
- A robust synthetic method for novel cyclic dinucleotides has been established.
- The butylene linkage offers a unique modification for potential therapeutic applications.
- This work expands the toolbox for synthesizing modified cyclic dinucleotides.