Synthesis of optically pure γPNA monomers: a comparative study
Arunava Manna1, Srinivas Rapireddy1, Gopalsamy Sureshkumar1
1Department of Chemistry and Center for Nucleic Acids Science and Technology (CNAST), Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213.
Tetrahedron
|February 23, 2019
Summary
Synthesizing chiral gamma-peptide nucleic acid (γPNA) monomers and oligomers is crucial. The Mitsunobu coupling method yields optically superior γPNA, unlike reductive amination which risks epimerization.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Biochemistry
Background:
- Chiral gamma-peptide nucleic acids (γPNAs) are important nucleic acid analogs.
- Efficient synthesis of optically pure γPNA monomers and oligomers is essential for their applications.
Purpose of the Study:
- To systematically compare reductive amination and Mitsunobu coupling for synthesizing chiral γPNA.
- To identify the optimal synthetic route for producing high-purity γPNA.
Main Methods:
- Investigated reductive amination and Mitsunobu coupling reactions.
- Utilized different protecting groups, including PhFl.
- Assessed epimerization levels and optical purity of products.
Main Results:
- Reductive amination is prone to epimerization, even under mild conditions.
- Bulky protecting groups like PhFl can minimize epimerization but are difficult to remove.
- Mitsunobu coupling yields optically superior γPNA products with standard carbamate protecting groups.
Conclusions:
- Mitsunobu coupling is the preferred method for synthesizing optically pure chiral γPNA monomers and oligomers.
- Reductive amination presents challenges due to epimerization, requiring careful optimization or alternative strategies.
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