Protected nucleosides which permit more efficient oligonucleotide syntheses

• US 4,980,460 A
• Filed: 03/30/1987
• Issued: 12/25/1990
• Est. Priority Date: 04/08/1986
• Status: Expired due to Term

• Current Assignee: Commissariat a L'Energie Atomique (AES Corporation)
• Original Assignee: Commissariat a L'Energie Atomique (AES Corporation)
• Inventors: Molko, Didier, Teoule, Robert, Schulhof, Jean-Claude
• Primary Examiner(s): Rollins, John W.
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US07/031,781
• Time in Patent Office: 1,366 Days
• Field of Search: 536/27, 536/28, 536/29
• US Class Current: 536/26.71
• 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

The invention relates to derivatives of nucleosides and their use for the synthesis of oligonucleotides.

These derivatives are in accordance with the formula: ##STR1## in which B represents a radical derived from guanine, cytosine or adenine, whose exocylic NH group is protected by the group ##STR2## with R¹ representing a hydrogen atom or an alkyl radical and R² a hydrogen atom, and alkyl radical, an alkoxy radical and optionally substituted aryloxy radical, R³ represents a hydrogen atom, the dimethoxytrityl radical or the radical ##STR3## R⁴ represents a hydrogen atom, the radical of formula: ##STR4## or a radical suitable for the synthesis of polynucleotides and R⁵ represents a hydrogen atom or the protected or unprotected hydroxyl OH radical.

Claims

1. A nucleoside having the formula:

wherein B is a divalent group chosen from among;

##STR33## connected to the CO group by its exocyclic NH group;

R¹ is hydrogen,

R² is a group selected from the group consisting of methoxy, phenoxy, chlorophenoxy and fluorophenoxy,

R³ is selected from the group consisting of hydrogen, 9-phenyl xanthenyl, trityl of formula;

##STR34## wherein R⁶, R⁷ and R⁸, which may be the same or different, are hydrogen, methyl, ethyl or methoxy, and the group ##STR35## wherein R¹ and R² have the meanings given above;

R⁴ is a hydrogen, a phosphorylated group selected from the group consisting of ##STR36## or the group ##STR37## wherein R¹ and R² have the meanings given above; and

R⁵ is a hydrogen or hydroxyl group.

2. The nucleoside of claim 1 wherein B is the divalent group of formula (II).

3. The nucleoside of claim 1 wherein B is the divalent group of formula (IV).

4. The nucleoside of claim 2 wherein R² is ##STR38##

5. The nucleoside of claim 3 wherein R² is phenoxy.

6. The nucleoside of claim 4 or claim 5 wherein R⁵ is hydrogen.

7. The nucleoside of claim 6 wherein R³ is ##STR39## and wherein R⁴ is ##STR40##

8. The nucleoside of claim 6 wherein R³ is ##STR41## and wherein R⁴ is ##STR42##

9. The nucleoside of claim 6 wherein R³ is ##STR43## and wherein R⁴ is ##STR44##

10. The nucleoside of claim 6 wherein R³ and R⁴ are hydrogen.

11. The nucleoside of claim 2 wherein R² is chlorophenoxy, R³, R⁴ and R⁵ are hydrogen.

12. The nucleoside of claim 6, wherein R³ is 4,4'"'"'-dimethoxytrityl and R⁴ is hydrogen.