Oligonucleotide Analogue Intermediate Synthesis for High Purity and Yield
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Solution Overview
Problem
The chemical synthesis of oligonucleotides is costly, cumbersome, and results in low-purity products, making it difficult for large-scale drug production and clinical research.
Innovation Solution
A method for preparing an oligonucleotide analogue involving a series of conversions using specific reducing agents, activators, and protecting groups to enhance purity and yield, including steps such as converting compounds of formulas II to VIII.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional chemical synthesis method is used for oligonucleotides, then the process is established and can produce oligonucleotides, but the production cost is high and the product purity is low
Solution Approach 1:
The patent changes the chemical reaction parameters by using specific reducing agents (sodium borohydride, borane-tetrahydrofuran complex) and activators (diisopropyl azodicarboxylate) to optimize the synthesis conditions. This transforms the conventional synthesis approach into a more selective process that achieves higher purity (95% or above) while maintaining cost-effectiveness through improved reaction efficiency and reduced purification requirements
Solution Approach 2:
The patent introduces specific intermediate compounds (compounds of formulas II, III, IV, V, VI, VII) with defined chemical structures as mediators in the synthesis pathway. These intermediates facilitate the formation of the final oligonucleotide product with high purity by enabling controlled stepwise reactions, avoiding the formation of unwanted byproducts that would require expensive purification
2Productivity
If conventional chemical synthesis method is used for oligonucleotides, then the process can produce oligonucleotides, but the process is cumbersome and product yield is low
Solution Approach 1:
The patent segments the synthesis process into distinct sequential steps with clearly defined intermediate compounds (formulas II through VII). Each step transforms one specific intermediate into the next, allowing for systematic optimization and scaling. This segmented approach simplifies the overall process by breaking down the complex synthesis into manageable stages with high individual yields that compound to high overall productivity
Solution Approach 2:
The patent optimizes reaction parameters including the use of specific solvents (dichloromethane, tetrahydrofuran), controlled temperatures, and stoichiometric ratios of reagents. These parameter changes enable each synthesis step to proceed with high efficiency and minimal side reactions, thereby increasing product yield while maintaining process simplicity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method provides a simpler, more economical, and high-yield process for producing oligonucleotide analogues, suitable for large-scale industrial applications.
Implementation Method 1
converting a compound of formula II into a compound of formula III in the presence of a reducing agent, wherein the reducing agent is sodium borohydride
Implementation Method 2
converting the compound of formula III into a compound of formula IV, wherein an activator is also added in the reaction process, and the activator is diisopropyl azodicarboxylate
Implementation Method 3
converting the compound of formula V into a compound of formula VI, wherein the reducing agent is Pd(OH)2/C
Data Source
AI summary
An intermediate for preparing an oligonucleotide analogue or a salt thereof, and a preparation method therefor. In particular, the present invention relates to a compound of formula VIII and a preparation method therefor. The definitions of substituents are as defined in the description.