# US 8,541,599 B2 · Supports for oligomer synthesis

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- Number: US 8,541,599 B2
- Document ID: US8541599B2
- Status: Granted
- Kind: B2
- Application number: 13/414,516
- Filed: 2012-03-07
- Published: 2012-06-28
- Granted: 2013-09-24
- Earliest claimed: 2003-02-01
- Assignees: Isis Pharmaceuticals, Inc.
- Applicants: Vasulinga Ravikumar; Muthiah Manoharan; Andrei P. Guzaev; Zhiwei Wang; Raju K. Kumar
- Inventors: Vasulinga Ravikumar; Muthiah Manoharan; Andrei P. Guzaev; Zhiwei Wang; Raju K. Kumar
- Web page: https://patentgrep.com/patent/US8541599B2

## CPC

- C07D 491/18: Bridged systems
- C07D 491/08: Bridged systems
- C07D 493/18: Bridged systems
- C07B 2200/11: Compounds covalently bound to a solid support
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

Universal linkers, their facile processes of manufacture and methods of using the same are provided.

## Claims

### Claim 1

A compound having the formula:
wherein:
one of Q1 and Q2 is a protecting group, a phosphodiester linked nucleoside or a phosphodiester linked oligonucleotide and the other of Q1 and Q2 is a linkage attached to a support medium; and
A is hydrogen, a blocking group, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aliphatic ether.

### Claim 2 (depends on 1)

The compound of claim 1 wherein A is an alkyl, alkenyl, alkynyl, substituted alkyl, substituted alkenyl or substituted alkynyl group.

### Claim 3 (depends on 1)

The compound of claim 1 wherein A is methyl.

### Claim 4 (depends on 1)

The compound of claim 1 wherein said linkage attached to a support medium has the formula:
—C(═O)—(CH2)n—C(═O)—
wherein n is from about 2 to about 8.

### Claim 5 (depends on 4)

The compound of claim 4 wherein n is 2.

### Claim 6 (depends on 1)

The compound of claim 1 wherein Q1 is a protecting group.

### Claim 7 (depends on 1)

The compound of claim 1 wherein Q2 is a protecting group.

### Claim 8 (depends on 1)

The compound of claim 1 wherein one of Q1 and Q2 is an acid labile hydroxyl protecting group.

### Claim 9 (depends on 8)

The compound of claim 8 wherein said acid labile hydroxyl protecting group is 4-methoxytriphenylmethyl, 4,4′-dimethoxytriphenylmethyl, 9-phenylxanthenyl or substituted 9-phenylxanthenyl.

### Claim 10 (depends on 9)

The compound of claim 9 wherein said acid labile hydroxyl protecting group is 4,4′-dimethoxytriphenylmethyl.

### Claim 11 (depends on 1)

The compound of claim 1 wherein one of Q1 and Q2 is a phosphodiester linked nucleoside or oligonucleotide.

### Claim 12 (depends on 1)

The compound of claim 1 wherein said support medium is controlled pore glass, oxalyl-controlled pore glass, silica-containing particles, polystyrene, copolymers of polystyrene and divinylbenzene, copolymers of dimethylacrylamide and N,N-bisacryloylethylenediamine, a soluble support medium or PEPS.

### Claim 13 (depends on 12)

The compound of claim 12 wherein said support medium is controlled pore glass, polystyrene or copolymers of polystyrene.

### Claim 14 (depends on 13)

The compound of claim 13 wherein said support medium is controlled pore glass.

### Claim 15 (depends on 1)

The compound of claim 1 wherein said support medium is HL30 Primer solid support, OligoPrep solid support, Nittomar 200 solid support or Nittomar 250 solid support.

### Claim 16 (depends on 1)

The compound of claim 1 wherein said linkage is attached to said support medium through an amide linkage.

### Claim 17 (depends on 1)

The compound of claim 1 having the formula:
wherein:
one of Q1 and Q2 is a protecting group, a phosphodiester linked nucleoside or a phosphodiester linked oligonucleotide and the other of Q1 and Q2 is a linkage attached to a support medium; and
A is hydrogen, a blocking group, a substituted or unsubstituted aliphatic group, or a substituted or unsubstituted aliphatic ether.

### Claim 18 (depends on 17)

The compound of claim 17 having the formula:
wherein:
SM is said support material;
A is hydrogen, a blocking group, a substituted or unsubstituted aliphatic group, or a substituted or unsubstituted aliphatic ether; and
Pg is an acid labile hydroxyl protecting group.

### Claim 19 (depends on 18)

The compound of claim 18 wherein:
A is alkyl; and
Pg is 4,4′-dimethoxytriphenylmethyl.

### Claim 20 (depends on 19)

The compound of claim 19 wherein A is methyl.

### Claim 21 (depends on 17)

The compound of claim 17 having the formula:
wherein:
SM is said support material;
A is hydrogen, a blocking group, a substituted or unsubstituted aliphatic group, or a substituted or unsubstituted aliphatic ether; and
Pg is an acid labile hydroxyl protecting group.

### Claim 22 (depends on 21)

The compound of claim 21 wherein:
A is alkyl; and
Pg is 4,4′-dimethoxytriphenylmethyl.

### Claim 23 (depends on 22)

The compound of claim 22 wherein A is methyl.

### Claim 24

A racemic mixture of compounds of the formula:
wherein:
A is alkyl or an aliphatic ether;
for the first percentage of the mixture Q3 is a protecting group and Q4 is SM-C(═O)—(CH2)2—C(═O)— and for the second percentage of the mixture Q3 is SM-C(═O)—(CH2)2—C(═O)— and Q4 is a protecting group and wherein the combined first and second percentages equal essentially 100 percent of the mixture.

### Claim 25 (depends on 24)

The racemic mixture of claim 24 wherein A is methyl.

### Claim 26 (depends on 25)

The racemic mixture of claim 25 wherein said protecting group is 4,4′-dimethoxytriphenylmethyl.