Methods for the synthesis of functionalized nucleic acids
US10280192B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Mar 30, 2018 |
| Grant date | May 7, 2019 |
| Priority date | — |
| Expiry date | Mar 30, 2038 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07H13/04
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
The present application, among other things, provides technologies, e.g., reagents, methods, etc. for preparing oligonucleotides comprising phosphorothiotriesters linkages. In some embodiments, provided methods comprise reacting an H-phosphonate of structure Ia or Ib with a silylating reagent to provide a silyloxyphosphonate, and reacting the silyloxyphosphonate with a thiosulfonate reagent of structure IIa or IIb to provide an oligonucleotide of structure IIIa or IIIb. In some embodiments, provided methods comprise reacting an H-phosphonate of structure Ic with a silylating reagent to provide a silyloxyphosphonate, reacting the silyloxyphosphonate with a bis(thiosulfonate) reagent of structure IVc to provide a phosphorothiotriester comprising a thiosulfonate group of structure Vc, and then reacting the phosphorothiotriester comprising a thiosulfonate group of structure Vc with a nucleophile of structure VIc to provide an oligonucleotide of structure IIIc. In some embodiments, the present application provides a thiosulfonate reagent of structure IIa:
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.