Process for the preparation of phosphorothioate triesters
First Claim
1. A process for the preparation of a phosphorothioate triester which comprises coupling an H-phosphonate with an alcohol in the presence of a coupling agent thereby to form an H-phosphonate diester, and subsequently, the H-phosphonate diester is reacted with a sulfur transfer agent thereby to form a phosphorothioate triester characterised in that the coupling reaction between the H-phosphonate and the alcohol, occurs in the presence of the sulfur transfer agent.
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Accused Products
Abstract
A process for the synthesis of a phosphorothioate triester is provided. The process comprises the coupling of an H-phosphonate with an alcohol in the presence of a solution comprising both a coupling agent and a sulfur transfer agent. Preferably, the H-phosphorate and alcohol are protected nucleosides or oligonucleotides.
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Citations
16 Claims
- 1. A process for the preparation of a phosphorothioate triester which comprises coupling an H-phosphonate with an alcohol in the presence of a coupling agent thereby to form an H-phosphonate diester, and subsequently, the H-phosphonate diester is reacted with a sulfur transfer agent thereby to form a phosphorothioate triester characterised in that the coupling reaction between the H-phosphonate and the alcohol, occurs in the presence of the sulfur transfer agent.
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15. A process for the preparation of a deprotected oligonucleotide, oligonucleotide phosphorothioate or mixed oligonucleotide/oligonucleotide phosphorothioate which comprises:
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a) coupling a protected nucleoside or oligonucleotide H-phosphonate comprising a 3′
or 5′
-H-phosphonate function with a protected nucleoside or oligonucleotide comprising a free 3′
or 5′
-hydroxy function in the presence of a coupling agent thereby to form an H-phosphonate diester and, in situ, reacting the H-phosphonate diester with a sulfur transfer agent to produce a phosphorothioate triester, wherein the coupling reaction between the H-phosphonate and the alcohol, occurs in the presence of the sulfur transfer agent; and
b) deprotecting the phosphorothioate triester produced in a) thereby to form a deprotected oligonucleotide, oligonucleotide phosphorothioate or mixed oligonucleotide, oligonucleotide/phosphorothioate. - View Dependent Claims (16)
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Specification