Process for the preparation of oligonucleotides
AssigneeAvecia Limited
InventorPaul McCormac
Life of this patent
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Abstract
A process for the synthesis of an oligonucleotide is provided in which an oligonucleotide is assembled on a swellable solid support using the phosphoramidite approach in the presence of an activator, wherein the activator is not tetrazole or a substituted tetrazole. Preferred activators are pyridinium, imidazolinium and benzimidazolinium salts; benzotriazole and derivatives thereof; and saccharin or a saccharin derivative. Preferred swellable solid supports comprise functionalised polystyrene, partially hydrolysed polyvinylacetate or poly(acrylamide).
Claims14
A process for the synthesis of an oligonucleotide in which an oligonucleotide is assembled on a swellable solid support using the phosphoramidite approach in the presence of an activator, wherein the activator is not tetrazole or a substituted tetrazole.
A process for the synthesis of an oligonucleotide which comprises coupling a nucleoside phosphoramidite with a nucleoside or oligonucleotide comprising a free hydroxy group in the presence of an activator, wherein:
- a) the nucleoside or nucleotide comprising a free hydroxy group is attached to a swellable solid support by a cleavable linker, said swellable support being selected from the group consisting of functionalized polystyrene, partially hydrolyzed polyvinylacetate and poly(acrylamide);
- b) said activator has the general chemical formula:
- wherein p is 0 or an integer from 1 to 4;
- R for each occurrence is a substituent, or two adjacent R groups taken together with the carbon atoms to which they are attached form a six membered saturated or unsaturated ring;
- and
- X is O or S;
- the employing a solvent which swells the solid support selected from the group consisting of acetonitrile, dimethylformamide, N-methylpyrrolidinone, dichloromethane, tetrahydrofuran and pyridine.
Dependencies are inferred from the claim text.