N-phthaloyl-protected 2'-amino-nucleoside phosphoramdites
AssigneeRibozyme Pharmaceuticals, Inc.
InventorsNassim Usman, David Sweedler, Leonid Beigelman
Life of this patent
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Abstract
A method for blocking the 2'-amino group of a nucleoside phosphoramidite using an N-phthaloyl protecting group. The 2'-amino-N-phthaloyl protected nucleotides are also disclosed.
Claims16
2'-deoxy-2'-amino-nucleoside phosphoramidite, wherein said 2'-amino group is protected by an N-phthaloyl protecting group.
Method for synthesizing protected 2'-deoxy-2'-amino-nucleoside phosphoramidite, comprising the steps of:
- a) treatment of a 2'-deoxy-2'-amino nucleoside with a reagent which protects the 3' and 5'-hydroxyl groups of said 2'-deoxy-2'-amino nucleoside;
- b) addition of an N-phthaloyl group to the amino at the 2'-position;
- c) deprotection of said 3' and 5' hydroxyl groups;
- d) tritylation at the 5' position;
- and
- e) phosphitylation at the 3' position,
- to provide a 5' protected, 2'-N-phthaloyl protected 2'-deoxy-2'-amino nucleoside phosphoramidite.
Method for synthesizing protected 2'-deoxy-2'-amino-nucleoside phosphoramidite, comprising the steps of:
- a) reaction of a 2'-deoxy-2'-amino nucleoside with N-carbethoxyphthalimide;
- b) desilylation;
- c) tritylation;
- and
- d) phosphitylation,
- to provide a 5' protected, 2'-N-phthaloyl protected 2'-deoxy-2'-amino nucleoside phosphoramidite.
Method for synthesizing protected 2'-deoxy-2'-amino-nucleoside phosphoramidite, comprising the steps of:
- a) drying of a 2'-deoxy-2'-amino nucleoside;
- b) reaction of said 2'-deoxy-2'-amino nucleoside with N-carbethoxyphthalimide;
- c) treatment of the resulting reaction mixture with CHCl.sub.3 and triethylamine;
- d) tritylation;
- and
- e) phosphitylation,
- to provide a 2'-N-phthaloyl protected 2'-deoxy-2'-amino nucleoside phosphoramidite.
Method for synthesizing protected 2'-deoxy-2'-amino-nucleoside phosphoramidite, comprising the steps of:
- (a) treatment of a 2'-deoxy-2'-amino nucleoside with a phthalamido-containing reagent to add a N-phthaloyl group to the amino at the 2' position;
- (b) tritylation at the 5' position;
- and
- (c) phosphitylation of the 3' position to provide a 5' protected 2'-N-phthaloyl protected 2'-deoxy-2'-amino nucleoside phosphoramidite.
Dependencies are inferred from the claim text.