Patent ID: 11814407

Abstract:
The present invention relates to methods of synthesis of stereodefined oligonucleotides wherein the protected 5′-hydroxy terminus of a nucleoside or oligonucleotide attached to a solid support is first unprotected, followed by coupling an oxazaphospholidine phosphoramidite monomer to the now deprotected 5′-hydroxy terminus, oxidizing the resultant phosphite triester intermediate with a sulfurizing reagent, and optionally washing the product. The method of synthesis of the present invention described above may be repeated to optionally elongate the stereodefined oligonucleotide being synthesized until the elongation cycle is intentionally terminated via deprotecting and cleavaging the resulting stereodefined oligonucleotide from the solid support. The oxazaphospholidine phosphoramidite monomer to be coupled in the present invention may optionally be chosen from Formula 1a and 1b. Generally, the present invention relates to enhanced synthesis methods wherein a single elongation cycle, optionally comprising repeated coupling and oxidation steps, results in an enhanced yield and higher purity of stereodefined phosphorothioate oligonucleotides.