# US 2026/0209244 A1 · Linker for nucleic acid synthesis, carrier, and methods for producing same

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- Number: US 2026/0209244 A1
- Document ID: US20260209244A1
- Status: Published application
- Kind: A1
- Application number: 19/141,961
- Filed: 2023-12-18
- Published: 2026-07-23
- Earliest claimed: 2022-12-20
- Assignees: SynCrest Inc.
- Applicants: SynCrest Inc.
- Inventors: Yoshiyuki HARI; Ryohei KAJINO
- Web page: https://patentgrep.com/patent/US20260209244A1

## CPC

- C07D 493/08: Bridged systems
- C07B 2200/11: Compounds covalently bound to a solid support
- 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
- 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)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)

## Abstract

An object of the present invention is to newly provide a linker for nucleic acid synthesis and a carrier for solid-phase nucleic acid synthesis. Provided are a linker precursor for nucleic acid synthesis, a linker for nucleic acid synthesis, and a carrier for solid-phase nucleic acid synthesis.

## Claims

### Claim 1

A method for producing a linker precursor for nucleic acid synthesis represented by the following formula (2);
wherein
in formula (2), A is present at one substitutable position and represents a —CO—OR group, a —NH—CO—OR group, or a —CO—NH—CH2—CO—OR group; and R represents a protecting group for carboxylic acids, and
in formula (2), B represents identically or differently, at a substitutable position, a hydrogen atom, a lower alkyl group, a lower alkoxy group, a cyano group, a nitro group, or a dialkylamino group;
the method comprising subjecting a compound represented by the following formula (1);
wherein in formula (1), A and B are the same as those in formula (2);
to an oxidation reaction in a solvent in the presence of an oxidizing agent and a reoxidizing agent.

### Claim 2 (depends on 1)

The production method according to claim 1, wherein the oxidizing agent is at least one oxidizing agent selected from the group consisting of osmium tetroxide (OsO4) and ozone (O3).

### Claim 3 (depends on 1)

The production method according to claim 1, wherein the reoxidizing agent is at least one reoxidizing agent selected from the group consisting of N-methylmorpholine-N-oxide (NMO), trimethylamine-N-oxide (Me3NO), and tert-butyl hydroperoxide (TBHP).

### Claim 4 (depends on 1)

The production method according to claim 1, wherein the solvent is a mixed solvent of water and a hydrophilic organic solvent.

### Claim 5

A linker precursor for nucleic acid synthesis represented by the following formula (2):
wherein
in formula (2), A is present at one substitutable position and represents a —CO—OR group, a —NH—CO—OR group, or a —CO—NH—CH2—CO—OR group; and R represents a protecting group for carboxylic acids, and
in formula (2), B represents identically or differently, at a substitutable position, a hydrogen atom, a lower alkyl group, a lower alkoxy group, a cyano group, a nitro group, or a dialkylamino group.

### Claim 6

A method for producing a linker precursor for nucleic acid synthesis represented by the following formula (3):
wherein
in formula (3), A is present at one substitutable position and represents a —CO—OR group, a —NH—CO—OR group, or a —CO—NH—CH2—CO—OR group; and R represents a protecting group for carboxylic acids,
in formula (3), B represents identically or differently, at a substitutable position, a hydrogen atom, a lower alkyl group, a lower alkoxy group, a cyano group, a nitro group, or a dialkylamino group, and
in formula (3), Prot1 represents a 4,4′-dimethoxytrityl group, a 4-methoxytrityl group, or a trityl group;
the method comprising reacting a compound represented by the following formula (2):
wherein in formula (2), A and B are the same as those in formula (3);
with 4,4′-dimethoxytrityl chloride (DMTr-Cl), 4-methoxytrityl chloride (MMTr-Cl), or trityl chloride (Tr-Cl) in a solvent.

### Claim 7 (depends on 6)

The production method according to claim 6, wherein the solvent is at least one organic solvent selected from the group consisting of aprotic polar solvents.

### Claim 8

A linker precursor for nucleic acid synthesis represented by the following formula (3):
wherein
in formula (3), A is present at one substitutable position and represents a —CO—OR group, a —NH—CO—OR group, or a —CO—NH—CH2—CO—OR group; and R represents a protecting group for carboxylic acids,
in formula (3), B represents identically or differently, at a substitutable position, a hydrogen atom, a lower alkyl group, a lower alkoxy group, a cyano group, a nitro group, or a dialkylamino group, and
in formula (3), Prot represents a 4,4′-dimethoxytrityl group, a 4-methoxytrityl group, or a trityl group.

### Claim 9

A method for producing a linker for nucleic acid synthesis represented by the following formula (4):
wherein
in formula (4), L is present at one substitutable position and represents a —CO—OH group, a —NH—CO—OH group, or a —CO—NH—CH2—CO—OH group,
in formula (4), B represents identically or differently, at a substitutable position, a hydrogen atom, a lower alkyl group, a lower alkoxy group, a cyano group, a nitro group, or a dialkylamino group,
in formula (4), Prot1 represents a 4,4′-dimethoxytrityl group, a 4-methoxytrityl group, or a trityl group, and
in formula (4), Prot2 represents a protecting group for hydroxyl groups;
the method comprising subjecting a compound represented by the following formula (3):
wherein
in formula (3), A is present at one substitutable position and represents a —CO—OR group, a —NH—CO—OR group, or a —CO—NH—CH2—CO—OR group; and R represents a protecting group for carboxylic acids, and
in formula (3), B and Prot1 are the same as those in formula (4);
to the following steps:
(1) performing hydrolysis in a solvent, and then
(2) protecting a hydroxyl group in a solvent.

### Claim 10 (depends on 9)

The production method according to claim 9, wherein the solvent used in step (1) is at least one solvent selected from the group consisting of alkaline aqueous solutions, ether-based solvents, alcohol-based solvents, and halogen-based solvents.

### Claim 11 (depends on 9)

The production method according to claim 9, wherein the solvent used in step (2) is at least one solvent selected from the group consisting of aprotic polar solvents and ether-based solvents.

### Claim 12

A linker for nucleic acid synthesis represented by the following formula (4);
wherein
in formula (4), L is present at one substitutable position and represents a —CO—OH group, a —NH—CO—OH group, or a —CO—NH—CH2—CO—OH group,
in formula (4), B represents identically or differently, at a substitutable position, a hydrogen atom, a lower alkyl group, a lower alkoxy group, a cyano group, a nitro group, or a dialkylamino group,
in formula (4), Prot1 represents a 4,4′-dimethoxytrityl group, a 4-methoxytrityl group, or a trityl group, and in formula (4), Prot2 represents a protecting group for hydroxyl groups.

### Claim 13

A method for producing a carrier for solid-phase nucleic acid synthesis represented by the following formula (5):
wherein
in formula (5), G is present at one substitutable position and represents the following formula (G1), (G2), or (G3),
in formula (G1), (G2), or (G3), SP represents a solid-phase carrier:
in formula (5), B represents identically or differently, at a substitutable position, a hydrogen atom, a lower alkyl group, a lower alkoxy group, a cyano group, a nitro group, or a dialkylamino group,
in formula (5), Prot1 represents a 4,4′-dimethoxytrityl group, a 4-methoxytrityl group, or a trityl group, and
in formula (5), Prot2 represents a protecting group for hydroxyl groups;
the method comprising reacting a compound represented by the following formula (4);
wherein
in formula (4), L is present at one substitutable position and represents a —CO—OH group, a —NH—CO—OH group, or a —CO—NH—CH2—CO—OH group, and
in formula (4), B, Prot1, and Prot2 are the same as those in formula (5);
with a solid-phase carrier represented by the following formula:
wherein SP represents a solid-phase carrier;
in a solvent in the presence of a coupling agent.

### Claim 14 (depends on 13)

The production method according to claim 13, wherein the coupling agent is at least one coupling agent selected from the group consisting of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU), 1-[bis(dimethylamino)methylene]-1H-benzotriazolium 3-oxide hexafluorophosphate (HBTU), O—(1H-6-chlorobenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide tetrafluoroborate (TATU), 1-[bis(dimethylamino)methylene]-1H-benzotriazolium 3-oxide tetrafluoroborate (TBTU), N,N′-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC-HCl), ethyl 2-cyano-2-((dimethyliminio)(morpholino)methyloxyimino)acetate hexafluorophosphate (COMU), diphenylphosphoryl azide (DPPA), 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), benzotriazol-1-yl-oxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP), and 1H-benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP).

### Claim 15 (depends on 13)

The production method according to claim 13, wherein the solvent is at least one organic solvent selected from the group consisting of aprotic polar solvents and halogen-based solvents.

### Claim 16

A carrier for solid-phase nucleic acid synthesis represented by the following formula (5):
wherein
in formula (5), G is present at one substitutable position and represents the following formula (G1), (G2), or (G3),
in formula (G1), (G2), or (G3), SP represents a solid-phase carrier:
in formula (5), B represents identically or differently, at a substitutable position, a hydrogen atom, a lower alkyl group, a lower alkoxy group, a cyano group, a nitro group, or a dialkylamino group,
in formula (5), Prot1 represents a 4,4′-dimethoxytrityl group, a 4-methoxytrityl group, or a trityl group, and
in formula (5), Prot2 represents a protecting group for hydroxyl groups.