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US 6,476,216 B1Granted
Preparation of phosphorothioate oligomers
AssigneeMcGill University
InventorsGeorge Just, Zhili Xin, Eric Marsault, Yi Jin, Jianchao Wang
Life of this patent
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Abstract
The present invention is directed to methods for solid phase nucleotide synthesis utilizing substituted imidazole catalysts.
Drawings
Claims26
A method for the preparation of an internucleotide linkage comprising the steps of:
- selecting a first nucleoside synthon having an activated phosphorus group;
- providing a second synthon having a free 5′-hydroxyl group, said second synthon being a mononucleoside synthon or a polynucleotide synthon;
- and
- reacting said first nucleoside synthon with said second synthon in the presence of a catalyst to form said internucleotide linkage;
- said catalyst having the formula:
- wherein:
- R12 and R13 are each independently halogen;
- and
- R14 is hydrogen, halogen, cyano, nitro, thio, alkyl having from one to 10 carbons, substituted alkyl having from one to 10 carbons, norbornyl, substituted norbornyl, aryl, substituted aryl wherein said substituents are electron withdrawing, or has the formula:
- wherein
- L is protecting group;
- provided that when R12 and R13 are each chlorine, R14 is not hydrogen;
- wherein said method is performed in solution or on a solid support.
10 more elements
A method for the preparation of an internucleotide linkage comprising the steps of:
- selecting a first nucleoside synthon having an activated phosphorus group;
- providing a second synthon, said second synthon being bound to a solid support, and having a free 5′-hydroxyl group, said second synthon being a mononucleoside synthon or a polynucleotide synthon;
- and
- reacting said first nucleoside synthon with said second synthon in the presence of a catalyst to form said internucleotide linkage;
- said catalyst having the formula:
- wherein:
- R12 and R13 are each independently halogen;
- and
- R14 is hydrogen, halogen, cyano, nitro, thio, alkyl having from one to 10 carbons, substituted alkyl having from one to 10 carbons, norbornyl, substituted norbornyl, aryl, substituted aryl wherein said substituents are electron withdrawing, or has the formula:
- wherein L is protecting group.
7 more elements
A method for solid phase nucleotide synthesis comprising the step of reacting a nucleoside phosphoramidite with the free 5′-hydroxyl group of a support-bound mononucleoside or polynucleotide in the presence of a catalyst to form an phosphite internucleoside linkage;
- wherein aid catalyst has the formula:
- wherein:
- R12 and R13 are each independently halogen;
- and
- R14 is hydrogen, halogen, cyano, nitro, thio, alkyl having from one to 10 carbons, substituted alkyl having from one to 10 carbons, norbornyl, substituted norbornyl, aryl, substituted aryl wherein said substituents are electron withdrawing, or has the formula:
- wherein L is protecting group.
3 more elements
A method comprising the steps of:
- reacting a nucleoside 3′-phosphoramidite with the free 5′-hydroxyl group of a support-bound mononucleoside or polynucleotide to form an phosphite internucleoside linkage;
- wherein said reaction is performed in the presence of a catalyst having the formula:
- wherein:
- R12 and R13 are each independently halogen;
- and
- R14 is hydrogen, halogen, cyano, nitro, thio, alkyl having from one to 10 carbons, substituted alkyl having from one to 10 carbons, norbornyl, substituted norbornyl, aryl, substituted aryl wherein said substituents are electron withdrawing, or has the formula:
- wherein L is protecting group.
4 more elements
Dependencies are inferred from the claim text.