Phosphorylation reagents for improved processes to convert...

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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C536S025310

Reexamination Certificate

active

10821631

ABSTRACT:
The present invention discloses novel phosphoramidite reagents for use in oligonucleotide synthesis. The present invention further discloses novel methods for the conversion of terminal hydroxyl groups of oligonucleotides into phosphate monoesters. By employing novel reagents, as also disclosed herein, the methods are fully compatible with standard procedures for solid phase oligonucleotide synthesis and do not require additional processing steps. The inventive reagents to phosphorylate terminal hydroxyl groups of oligonucleotides are superior to the prior art in that they for the first time combine the desired attributes of being a solid compound for facile handling, comprising two β-eliminating protective groups removable as fast or faster than the standard cyanoethyl group, providing a DMT-group for easy monitoring of the coupling efficiency, and enabling a fast final deprotection of the phosphorylated oligonucleotide without any extra manipulation steps.

REFERENCES:
patent: 5252760 (1993-10-01), Urdea et al.
patent: 5959090 (1999-09-01), Guzaev et al.
Connolly (1987) Tetrahedron Letters 28:463-466.
Guzaev et al. (1995) Tetrahedron 51:9375-9384.
Guzaev et al. (1999) Tetrahedron 55:9101-9116.
Guzaev et al. (2001) Tetrahedron Letters 42:4769-4773.
Horn and Urdea (1986) Tetrahedron Letters 27:4705-4708.
Schwarz and Pfleiderer (1987) Nucleosides & Nucleotides 6:537-539.
Uhlmann and Engels (1986) Tetrahedron Letters 27:1023-1026.

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