초록

Methods and Intermediates for the Preparation of Oligomers Containing Diastereomerically Enriched Phosphorothioate Linkages are Disclosed.

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1. 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;

1. 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 the presence of a catalyst to form said internucleotide linkage; said catalyst having the formula: ?wherein: R14 is 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 a protecting group; wherein said method is performed in solution or on a solid support.2. The method of claim 1 wherein said first nucloeside synthon is a nucleoside phosphoramidite.3. The method of claim 2 wherein said second synthon is nucleoside phosphoramidite.4. The method of claim 1 wherein said internuciotide linkage is a phosphite linkage.5. The method of claim 1 further comprising the step of oxidizing said internucleotide linkage to form a phosphodiester linkage, a phosphorothiate linkage, or a phosphorodithioate linkage.6. The method of claim 1 wherein said catalyst has the structure: wherein R14 is halogen, cyano, nitro, thio, alkyl having from one to 10 carbons, substituted alkyl having from one to 10 carbons, aryl, or substituted aryl wherein said substituents are electron withdrawing.7. The method of claim 1 wherein R14 is halogen, cyano, nitro, thio, or alkyl having from one to 10 carbons.8. The method of claim 7 wherein R14 is cyano.9. The method of claim 7 wherein R14 is halogen.10. The method of claim 9 wherein R14 is bromine.11. The method of claim 5 wherein said catalyst has the structure: wherein R14 is halogen, cyano, nitro, thio, alkyl having from one to 10 carbons substituted alkyl having from one to 10 carbons, aryl, or substituted aryl wherein said substituents are electron withdrawing.12. The method of claim 11 wherein R14 is halogen, cyano, nitro, thio, or alkyl having from one to 10 carbons.13. The method of claim 12 wherein R14 is cyano.14. The method of claim 12 wherein R14 is halogen.