Purine nucleoside modifications by palladium catalyzed methods and oligonucleotides containing same

• US 5,783,679 A
• Filed: 05/16/1995
• Issued: 07/21/1998
• Est. Priority Date: 06/14/1993
• Status: Expired due to Term

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: NeXstar Pharmaceuticals, Inc. (Gilead Sciences Inc.)
• Inventors: Eaton, Bruce, Tu, Chi
• Primary Examiner(s): Wilson, James O.
• Application Number:
  US08/441,881
• Time in Patent Office: 1,162 Days
• Field of Search: 536/26.7, 536/26.71, 536/26.72, 536/27.14, 536/27.6, 536/27.81, 536/23.1, 536/27.21, 514/45, 514/46, 514/47, 514/48, 514/43
• US Class Current: 536/23.1
• CPC Class Codes: B01J 2231/4255 Stille-type, i.e. RY + R'3SnR'', in which R is alkenyl, aryl, R' is alkyl and R'' is alkenyl or aryl
• CPC Class Codes: B01J 2531/824 Palladium
• CPC Class Codes: B01J 31/2404 Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Abstract

This invention discloses an improved method for the preparation modified purine nucleosides at the 2-, 6- or 8-position of the purine ring, using a palladium catalyst.

Claims

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

a) preparing a solution of a palladium catalyst of the formula PdL₃, wherein L is a ligand of palladium;

b) reacting a purine starting material containing a halogen leaving group attached to the 8-position of said purine starting material with an organotin compound of the formula R² SnR¹₃, and R² displaces the leaving group from the purine starting material, wherein R¹ is a C1 to C15 alkyl, and R² is a C1 to C15 alkyl or a C1 to C15 alkenyl, in the presence of the palladium catalyst; and

c) isolating and purifying said purine nucleoside.

2. A compound of the formula:

##STR17## wherein R² is a C1 to C15 alkyl or a C1 to C15 alkenyl, either of which may be optionally substituted with a member of the group consisting of alcohols, ethers, ketones, esters, amides, amines, C1 to C15 alkanes, C1 to C15 alkenes, sulfides and disulfides; and

Z is selected from the group consisting of a ribose, deoxyribose and dideoxyribose.

3. The compound of claim 2 wherein R² is a substituted or unsubstituted vinyl.

4. The compound of claim 3 wherein R² is ##STR18## wherein Y₁, Y₂ and Y₃ are independently selected from the group consisting of protected alcohols, ethers, ketones, aldehydes, esters, amides, amines, C1 to C15 alkanes, C1 to C15 alkenes, C1 to C15 alkynes, and sulfides.

5. The compound of claim 2, incorporated as part of a oligonucleotide.

6. The compound of claim 5 wherein said oligonucleotide is a ribonucleic acid.

7. The compound of claim 5 wherein said oligonucleotide is a deoxyribonucleic acid.