Nucleoside modifications by palladium catalyzed methods

• US 20040034212A1
• Filed: 01/24/2003
• Published: 02/19/2004
• Est. Priority Date: 09/25/1998
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Tu, Chi, Beckvermit, Jeffrey T.
• Granted Patent: US 6,846,918 B2
• Time in Patent Office: Days
• US Class Current: 536/26.1
• CPC Class Codes: C07H 19/06 Pyrimidine radicals

Abstract

This invention discloses a method for the preparation of 2′-modified nucleosides, using a palladium catalyst and an alkene functionalized with a heteroatom. Included in the invention are the novel pyrimidines and purines that can be prepared according to the method of the invention and oligonucleotides containing said modified pyrimidines and purines.

Claims

1. Purine nucleosides or purine nucleotides modified at the 2-, 6- or 8-position of the purine ring prepared according to a method comprising comprising the steps of:

reacting a purine starting material containing a leaving group attached to the 2-, 6- or 8-position of said purine starting material with a functionalized alkene having the formula;

 

wherein

Y is selected from the group consisting of —

CHROH, —

C(O)R, —

COOR, —

C(O)NRR′

, —

CN, a substituted or unsubstituted aryl group or heterocylic group, selected from the group consisting of phenyl, 2-, 3- or 4-hydroxyphenyl, 2-, 3- or 4-pyridyl and 1H-tetrazol-5-yl;

R and R′

are independently selected from the group consisting of H, substituted or unsubstituted alkyl, alkenyl and aryl; and

n is an integer from 0-15

in the presence of a palladium catalyst of the general formula PdL₃ or PdL₄, wherein L is a ligand of palladium; and

isolating said modified nucleoside or nucleotide.