US 5,859,233 A · Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates

Abstract

The invention provides a method of synthesizing oligonucleotide N3'.fwdarw.P5' phosphoramidates using an amine-exchange reaction of phosphoramidites in which a -deprotected 3'-amino group of a solid phase supported oligonucleotide chain is exhanged for the amino portion of a 5'-phosphoramidite of an incoming monomer which has a protected 3'-amino group. The resulting internucleotide phosphoramidite linkage is then oxidized to form a stable protected phosphoramidate linkage. The method of the invention greatly improves product yields and reduces reagent usage over currently available methods for synthesizing the above class of compound.

Claims8

Dependent claims

A compound of the formula:

##STR14## wherein:
B is pyrimidine, purine, or an analog thereof;
R.sup.1 is a phosphate protecting group;
W is --NHR.sup.2, where R.sup.2 is an amino protecting group and;
R.sup.3 is hydrogen, hydroxyl, fluoro or --OR', where R' is alkyl having from 1 to 3 carbon atoms or a hydroxyl protecting group;
and
R.sup.4 and R.sup.5 together with the nitrogen to which they are attached form an alkylamino- or arylamino leaving group having up to 40 atoms selected from the group consisting of carbon, oxygen, sulfur, and nitrogen.

4 more elements

Dependencies are inferred from the claim text.

Facts

Application

08/771,789Filed 20 Dec 1996 · continuation in part

Priority

21 Feb 1996

Granted

12 Jan 1999

Term ends

Not estimatedThe source records don’t support an estimate.

Classification4 codes

C07H 19/10
Pyrimidine radicals: with the saccharide radical esterified by phosphoric or polyphosphoric acids
C07H 19/20
Purine radicals: with the saccharide radical esterified by phosphoric or polyphosphoric acids
C07H 21/00
Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate
C07H
Sugars

Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates

Life of this patent

Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates

Life of this patent

Abstract

Claims8