Synthesis of oligomeric compounds comprising phosphorothioate diester and phosphodiester linkages
AssigneeIonis Pharmaceuticals, Inc.
InventorsAndrew K. McPherson, Andrew A. Rodriguez, Daniel C. Capaldi
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Abstract
The present disclosure provides methods for synthesizing oligomeric compounds having at least one phosphorothioate diester linkage and at least one phosphate diester internucleoside linkage. In certain embodiments, the present disclosure provides oxidation reagents that produce low amounts of unwanted phosphate diester impurities in oligomeric compounds having at least one phosphorothioate diester linkage and at least one phosphate diester internucleoside linkage.
Claims13
A process for synthesizing an oligomeric compound comprising an oligonucleotide, comprising contacting a first oligonucleotide intermediate having a phosphite triester linkage with an oxidizing agent to form a second oligonucleotide intermediate having a phosphate triester linkage;
- wherein the oxidizing agent consists of a mixture of 12, a halide salt, pyridine, and water, and wherein the concentration of I2 is 0.05 M and the concentration of the halide salt is 0.05 M;
- wherein the halide salt is selected from NaI, KI, or LiI.
Dependencies are inferred from the claim text.