Solution-based method of making oligonucleotides via phosphoramidite coupling
US9029528B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | May 17, 2012 |
| Grant date | May 12, 2015 |
| Priority date | — |
| Expiry date | Feb 15, 2033 |
Classification
- Technology area (CPC Y)Emerging Cross-Sectional Technologies
- CPC primaryY02P20/55
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
A method of producing an n+p-mer oligonucleotide efficiently in a high yield, which includes use of, as a starting material, an n-mer oligonucleotide wherein the 3′-terminal hydroxyl group is protected, and the 5′-terminal hydroxyl group is protected by a temporary protecting group, and continuously performing, in a solution, (1) a deprotection step of the 5′-terminal hydroxyl group, (2) a 5′-terminal elongation step by the addition of a p-mer oligonucleotide wherein the 3′-position is phosphoramidited, and (3) an oxidation step or a sulfurization step of a phosphite triester moiety. The 3′-hydroxyl group of the n-mer oligonucleotide is protected by a solubilizing protecting group represented by formula: -L-Y—Z, where L is a group represented by formula (a1):Y is an oxygen atom, or NR wherein R is a hydrogen atom, an alkyl group or an aralkyl group, and Z is a group represented by formula (a2):
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.