Compounds

• US 5,681,945 A
• Filed: 04/05/1993
• Issued: 10/28/1997
• Est. Priority Date: 04/03/1992
• Status: Expired due to Term

• Current Assignee: Nitto Denko Avecia, Inc. (Nitto Denko Corporation)
• Original Assignee: Zeneca Incorporated (Astrazeneca PLC)
• Inventors: Garman, Andrew John, McLean, Michael Joseph
• Primary Examiner(s): Lilling, Herbert J.
• Application Number:
  US08/041,591
• Time in Patent Office: 1,667 Days
• Field of Search: 536/25.3, 536/25.6, 536/26.1, 536/25.34
• US Class Current: 536/25.34
• CPC Class Codes: C07D 307/20 Oxygen atoms
• 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: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

A support carrying a homocyclic or heterocyclic ring containing a first and second carbon atom wherein: (i) the first carbon atom is substituted by a nucleophilic group or a group convertible to a nucleophilic group on treatment with base; (ii) the second carbon atom is substituted by a hydroxy group, a hydroxy group protected by an acid labile protecting group, or a phosphate group substituted by an oligonucleotide; and (iii) the first and second carbon atoms are directly connected by a covalent bond; which is suitable for use in oligonucleotide synthesis. Methods for its preparation and use, and novel compounds for attachment to the support are described.

Claims

1. A support carrying a cyclopentyl ring, a cyclohexyl ring or a heterocyclic ring consisting of 4 or 5 carbon atoms and 1 nitrogen, sulphur or oxygen atom, said ring including a first and a second carbon atom wherein:

(i) said first carbon atom is substituted by a nucleophilic group selected from the class consisting of an amino group, a thio group and a hydroxy group, or an ester group convertible to a nucleophilic group on treatment with base;

(ii) said second carbon atom is substituted by a hydroxy group protected by an acid labile protecting group, or a phosphate group substituted by an oligonucleotide;

(iii) the first and second carbon atoms are directly connected to one another by a covalent bond;

(iv) said ring is coupled to the support through said first carbon atom or through said nucleophilic group or group convertible to said nucleophilic group on said first carbon atom; and

(v) said ring optionally being further substituted on any one or more carbon atom other than said first and second carbon atoms.

2. A support according to claim 1 wherein the support carries a group of formula (2) ##STR38## wherein A and B are said first and second carbon atoms, respectively;

Z² is an acid labile protecting group, or a phosphate group substituted by an oligonucleotide; and

n is 1.

3. A support according to claim 1 or 2 wherein said heterocyclic ring is a pyran or furan ring free from double bonds.

4. A support according to claim 1 or 2 wherein said one or more optional ring carbon substituent is independently selected from hydroxy;

a group convertible to hydroxy on treatment with base;

straight or branched chain C_1-6 alkyl;

C_1-6 alkoxy;

aryloxy;

halogen;

cyano; and

nitro.

5. A support according to claim 2 wherein Z² is an acid labile protecting group selected from the group consisting of tetrahydropyranyl groups;

optionally substituted trityl groups;

pixyl;

isobutyloxycarbonyl;

t-butyl; and

dimethylsilyl.

6. A support according to claim 5 wherein Z² is monomethoxytrityl or dimethoxytrityl.

7. A support according to claim 2 wherein:

A and B are carbon atoms of an optionally substituted 5- or 6-membered ring selected from pyran and furan rings free from double covalent bonds, and cyclohexyl and cyclopentyl rings;

Z² is monomethoxytrityl or dimethoxytrityl;

n is 1; and

said one or more optional ring carbon substituent is independently selected from hydroxy;

straight and branched chain C_1-6 alkyl;

C_1-6 alkoxy;

aryloxy;

halogen;

cyano;

nitro;

thio; and

amino.

8. A support according to claim 2 wherein the group of Formula (2) is selected from formulae 1(b), 1(c) and 1(d):

##STR39## wherein A is said first carbon atom;

B is said second carbon atom, and Z¹ is an acid labile protecting group.

9. A support carrying a group selected from the formulae ##STR40## wherein DMT is 4,4'"'"'-dimethoxytrityl.