Abstract: Provided herein are solid phase methods for the synthesis of conjugated oligomeric compounds and intermediates used in such methods. In particular, the solid phase methods provide for addition of a phosphoramidite functionalized conjugate group to a solid support bound oligomeric compound. The methods also provide an increase in overall yield and a cost benefit over existing methods.

Abstract: Provided herein are solid phase methods for the synthesis of conjugated oligomeric compounds and intermediates used in such methods. In particular, the solid phase methods provide for addition of a phosphoramidite functionalized conjugate group to a solid support bound oligomeric compound. The methods also provide an increase in overall yield and a cost benefit over existing methods.

Abstract: Provided herein are methods for the synthesis of oligomeric compounds wherein the standard coupling protocols are modified when coupling bicyclic nucleosides of Formula I. More particularly, the modified coupling protocols provide for a decrease in the ratio of phosphoramidite solution to activator solution in the coupling reagent with an increased contact time. The modified coupling protocols provide for oligomeric compounds having comparable yields to similar oligomeric compounds having modified nucleosides other than bicyclic nucleosides of Formula I.

Abstract: Provided herein are methods for the solid phase synthesis of oligomeric compounds wherein at least one of the capping steps has been modified. More particularly, methods are provided wherein one or more of the capping steps is omitted or performed using reduced equivalents of acetic anhydride. In certain embodiments, the methods provide an enhanced purity profile. In certain embodiments, the methods provide an increased yield. The methods provided herein also provide at least an economic advantage over currently used methods in that reduced amounts of the mixture of capping reagents are required.

Abstract: Provided herein are methods for the synthesis of oligomeric compounds wherein the standard coupling protocols are modified when coupling bicyclic nucleosides of Formula I. More particularly, the modified coupling protocols provide for a decrease in the ratio of phosphoramidite solution to activator solution in the coupling reagent with an increased contact time. The modified coupling protocols provide for oligomeric compounds having comparable yields to similar oligomeric compounds having modified nucleosides other than bicyclic nucleosides of Formula I.

Abstract: Provided herein are methods for the solid phase synthesis of oligomeric compounds wherein at least one of the capping steps has been modified. More particularly, methods are provided wherein one or more of the capping steps is omitted or performed using reduced equivalents of acetic anhydride. In certain embodiments, the methods provide an enhanced purity profile. In certain embodiments, the methods provide an increased yield. The methods provided herein also provide at least an economic advantage over currently used methods in that reduced amounts of the mixture of capping reagents are required.

Abstract: The present invention relates to apparatus and methods for synthesizing oligonucleotides wherein a reaction zone has a variable volume based on the position of a piston, and the piston is adjusted to control the amount of headspace above solid support in the reaction zone. Methods and apparatus that limit the size or existence of the headspace are described.

Abstract: The present invention relates to apparatus and methods for synthesizing oligonucleotides wherein a reaction zone has a variable volume based on the position of a piston, and the piston is adjusted to control the amount of headspace above solid support in the reaction zone. Methods and apparatus that limit the size or existence of the headspace are described.