Nucleic Acid Oligomer Oxidation With Heat-Treated Iodine Solution
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Solution Overview
Problem
Existing methods for synthesizing nucleic acid oligomers, such as DNA and RNA, are inefficient and result in unsatisfactory purity, particularly in the conversion of phosphite triester bonds to phosphate triester bonds during the oxidation step.
Innovation Solution
A heat-treated oxidation solution containing iodine, pyridine, and water is used to convert phosphite triester bonds to phosphate triester bonds in the synthesis of nucleic acid oligomers, optimizing the process through specific concentration and solvent mixtures, including acetonitrile and tetrahydrofuran, and aging the solution before use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional oxidation solution is used to convert phosphite triester bonds to phosphate triester bonds, then the synthesis process can be completed, but the purity of the nucleic acid oligomer is not satisfactory
Solution Approach 1:
The patent applies parameter changes by modifying the oxidation solution's composition and temperature parameters. Specifically, it uses a oxidation solution containing iodine, pyridine, and water heated to 40°C or higher, which optimizes the conversion of phosphite triester bonds to phosphate triester bonds and improves the purity of the resulting nucleic acid oligomer.
Solution Approach 2:
The patent employs strong oxidation by using iodine as the oxidizing agent in the oxidation solution. This accelerated oxidation process efficiently converts phosphite triester bonds to phosphate triester bonds, enhancing both the purity and efficiency of the nucleic acid oligomer synthesis.
2Manufacturing precision
If the oxidation step is performed with standard conditions, then the process is simple, but the conversion of phosphite triester bonds to phosphate triester bonds is incomplete
Solution Approach 1:
The patent modifies the oxidation solution parameters by incorporating specific components (iodine, pyridine, water) and controlling temperature (40°C or higher), which enhances the conversion efficiency of phosphite triester bonds to phosphate triester bonds while maintaining practical process simplicity.
Solution Approach 2:
The patent uses pyridine as an intermediary substance in the oxidation solution, which facilitates the conversion of phosphite triester bonds to phosphate triester bonds by mediating the reaction between iodine and the phosphite ester, thereby improving conversion efficiency.
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
This process enhances the purity of nucleic acid oligomers by effectively converting phosphite triester bonds to phosphate triester bonds, improving the overall efficiency and quality of nucleic acid synthesis.
Implementation Method 1
a heat-treated oxidation solution which contains iodine, water and pyridine is used as an oxidation solution in an oxidation of phosphite ester which is produced by a coupling reaction using phosphoramidite
Data Source
AI summary
The present invention provides an efficient process for preparing a nucleic acid oligomer, that is, a process for preparing a nucleic acid having a phosphate triester bond effectively by oxidizing a nucleic acid precursor having a phosphite triester bond. Specifically, the present invention provides a process for preparing a nucleic acid compound having at its 5′-terminus a nucleotide represented by formula (I) by a phosphoramidite method, which comprises a step of reacting a precursor having a phosphite triester bond represented by a formula (II) (the definitions of substituents of formulae (I) and (II) are described in the Description) with an oxidation solution subjected to a heat-treatment that contains iodine, pyridine and water.