2,N.sup.6 -disubstituted and 2,N.sup.6 -trisubstituted adenosine-3'-phosphoramidites

• US 4,845,205 A
• Filed: 01/08/1986
• Issued: 07/04/1989
• Est. Priority Date: 01/08/1985
• Status: Expired due to Fees

• Current Assignee: Centre National De La Recherche Scientifique, Institut Pasteur
• Original Assignee: Centre National De La Recherche Scientifique, Institut Pasteur
• Inventors: Igolen, Jean, Huynh Dinh, Tam, Gouyette, Catherine
• Primary Examiner(s): Griffin, Ronald W.
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US06/822,639
• Time in Patent Office: 1,273 Days
• Field of Search: 536/27, 536/28
• US Class Current: 536/25.34
• 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
• CPC Class Codes: C12Q 1/68 involving nucleic acids

Abstract

The invention concerns 2,N⁶ -disubstituted and 2,N⁶ -trisubstituted adenosine nucleosides in which the sugar component is substituted at position 3'"'"' or position 5'"'"' by a phosphite or phosphoramidite group of the formula: ##STR1## R₁ representing a lower alkyl or --(CH₂)_n --CN with n being an integer between 1 and 4, and X representing a halogen or an amine group. These nucleosides make it possible to prepare sequences of nucleotides usable, in particular, as probes in the field of analyses and biological extractions.

Claims

1. Adenosines having the formula:

##STR15## in which one of --OR₇ and --OR₈ is a phosphite or a phosphoramidite group of the formula ##STR16## and the other of --OR₇ and --OR₈ or --OR₄, and wherein;

R₁ is a lower alkyl radical or --(CH₂)_n --CN, n being an integer of from 1 to 4;

X is a halogen atom, an amino group, or a member selected from the group consisting of tetrazolyl, imidazolyl, nitroimidazolyl, indolyl, pyrazolyl, benzimidazolyl, isoindolyl, pyrrolyl, triazolyl, dioxazolyl, dialkylamino, morpholino, pyrrolidino and piperidino groups;

R₄ is a hydroxyl protecting group;

R₂ is --NH(A₁) or --N(A₁, A₂);

R₃ is --NH(A₁), --N(A₁, A₂), --O(A₁) or --S(A₁);

A₁ and A₂ are identical or different and are selected from the group consisting of hydrogen and acyl groups;

R₅ is a hydrogen atom or a group --OR₆, wherein R₆ is hydrogen, an acyl group or a hydroxyl protecting group.

2. Adenosines according to claim 1, wherein R₁ represents a methyl group.

3. Adenosines according to claim 1, wherein R₁ represents --(CH₂)₂ --CN.

4. Adenosine according to claim 1, wherein X is a chlorine atom, a bromine atom, or a member selected from the group consisting of dimethylamino, diethylamino, dipropylamino, diispropylamino, morpholino, pyrrolidino, 2,2,6,6-tetramethylpiperidino, tetrazolyl, imidazolyl, nitroimidazolyl, indolyl, pyrazolyl, benzimidazolyl, isoindolyl, pyrrolyl, triazolyl, and dioxazolyl groups.

5. Adenosines according to claim 1, wherein A₁ and A₂, which are identical or different, are acyl groups selected from the group consisting of acetyl, benzoyl, butyryl and isobutyryl.

6. Adenosines according to claim 1, wherein R₄ is a protecting group selected from the group consisting of the radicals trityl, methoxytrityl, dimethoxytrityl, dialkoxylphosphite, pivalyl, isobutyloxy carbonyl and t-butyl-dimethylsilyl.