Isis Pharmaceuticals, Inc.

Hoechst Marion Roussel

Marion Merrell Dow Inc.

Aventis Pharmaceuticals Inc.

Douglas L Cole

Vasulinga T Ravikumar

Zacharia S Cheruvallath

Daniel C Capaldi

David R Borcherding

Ronald E Esser

Carl K Edwards, Iii

Muthiah Manoharan

Andrei P Guzaev

Achim H Krotz

Dennis Mulvey

Richard Holmes Griffey

Phillip Dan Cook

Mark Andrade

Carl K Edwards

Carl Edwards, Iii

Achim Krotz

Methods for the formation of sulfurized oligonucleotides are provided. The methods allow for the formation of phosphorothioate linkages in the oligonucleotides or derivatives, without the need for complex solvent mixtures and repeated washing or solvent changes. Oligonucleotides having from about 8, and up to about 50, nucleotides can be sulfurized according to the methods of the invention with higher yields than have been previously reported.

Synthesis of sulfurized oligonucleotides

Synthetic processes are provided wherein oligomeric compounds are prepared having phosphodiester, phosphorothioate, phosphorodithioate, or other covalent linkages. The oligomers have substantially reduced exocyclic adducts deriving from acrylonitrile or related contaminants.

Process for the synthesis of oligomeric compounds

Synthetic processes are provided for the solution phase synthesis of oligonucleotides, especially phosphorothioate oligonucleotides, and intermediate compounds useful in the processes. Intermediates having structureare prepared in accord with preferred embodiments.

Synthesis of oligonucleotides

Synthetic processes are provided wherein oligomers are prepared using phosphoramidite compositions. Oligomers having phosphodiester, phosphorothioate, phosphorodithioate covalent linkages are prepared that can include other covalent linkages. Also provided are compositions useful in such processes.

Oligomer phosphoramidite compositions and processes for synthesizing the same

This invention presents novel methods for synthesizing phosphorothioate oligonucleotides, using support-bound phosphoramidites. Novel intermediates useful in the methods are also provided.

Diribonucleoside Phosphoramidites

Synthetic processes are provided wherein oligomeric compounds are prepared having phosphodiester, phosphorothioate, phosphorodithioate, or other covalent linkages. Also provided are synthetic intermediates useful in such processes.

Intermediates for the synthesis of oligonucleotide analogues

Synthetic processes are provided wherein high purity oligomers are prepared using support bound phosphoramidite protocols starting with a nucleoside or larger synthon linked to a support media through a nucleosidic heterocyclic base moiety. Intermediates undergoing depurination at the support linkage site are removed during the wash cycle. Also provided are compositions useful in such processes.

Process for the preparation of oligonucleotide compounds

Processes for the synthesis of oligomers using phosphoramidite compositions

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San Diego, CA, United States of America

Douglas L Cole