Modified Nucleoside Phosphoramidites for High-Purity Oligonucleotide Synthesis
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Solution Overview
Problem
There is a need for improved synthetic methods to produce high-purity modified oligonucleotides with diverse modifications, capable of being synthesized at higher yields and volumes to meet the demand for custom-made oligonucleotides.
Innovation Solution
Development of novel 5'-phosphoramidite nucleoside monomers represented by Formulas (I) and (II), which can be used to synthesize modified oligonucleotides, with specific structures and protecting groups, and compositions comprising these monomers with high purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional synthetic methods are used to produce modified oligonucleotides, then the synthesis can be performed with existing monomers, but the purity and yield are insufficient to meet therapeutic demand
Solution Approach 1:
The patent modifies the chemical structure of nucleoside monomers by introducing specific substituents at the 2' position (such as methoxyethyl groups) and using protected nucleobases, which changes the reaction parameters and enables higher purity and yield in oligonucleotide synthesis
Solution Approach 2:
The invention creates composite monomer structures combining modified sugar moieties (with 2' substitutions) with protected nucleobases and phosphoramidite groups, resulting in monomers that simultaneously provide high purity, high yield, and diverse modification capabilities
2Adaptability or versatility
If existing monomers are used for oligonucleotide synthesis, then the process is straightforward, but the diversity of modifications is limited
Solution Approach 1:
The patent divides the nucleoside structure into separable functional components (sugar moiety with 2' substitution, nucleobase, and phosphoramidite group) that can be independently modified and recombined, enabling diverse oligonucleotide sequences and modifications while maintaining a systematic synthetic approach
Solution Approach 2:
The modified nucleoside monomers serve multiple functions: they provide the backbone structure for oligonucleotide formation, incorporate diverse 2' substitutions for therapeutic stability, include protected nucleobases for sequence variability, and contain phosphoramidite groups for automated synthesis compatibility
Data Source
AI summary
The present disclosure relates to compounds and compositions containing 5′-phosphoramidite nucleoside monomers, and methods of making and use.