# US 2019/0169223 A1 · Oligonucleotide production method

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2019/0169223 A1
- Document ID: US20190169223A1
- Status: Published application
- Kind: A1
- Application number: 15/776,709
- Filed: 2016-11-17
- Published: 2019-06-06
- Earliest claimed: 2015-11-17
- Assignees: Nissan Chemical Corporation
- Applicants: Nissan Chemical Corporation
- Inventors: Yudai SUGAWARA
- Web page: https://patentgrep.com/patent/US20190169223A1

## CPC

- C07H 21/04: with deoxyribosyl as saccharide radical
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07H 1/00: Processes for the preparation of sugar derivatives
- C07H 19/10: with the saccharide radical esterified by phosphoric or polyphosphoric acids
- C07H 19/20: with the saccharide radical esterified by phosphoric or polyphosphoric acids
- C07H 21/02: with ribosyl as saccharide radical
- Y02P 20/55: Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- 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)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- Y02P: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS

## Abstract

The invention provides a novel method for producing an oligonucleotide using a nucleoside or oligonucleotide that is easy to isolate and has high storage stability. The oligonucleotide production method includes a step of subjecting a nucleoside or oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of 2′-position, 3′-position, 5′-position and a nucleobase moiety and having a 5′-hydroxyl group or a 3′-hydroxyl group, to H-phosphonation to convert the 5′-hydroxyl group or the 3′-hydroxyl group into an H-phosphonated form.

## Claims

### Claim 1

A production method of an oligonucleotide comprising a step of subjecting a 5′-hydroxyl group or 3′-hydroxyl group of a nucleoside or oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of 2′-position, 3′-position, 5′-position and a nucleobase moiety and having a 5′-hydroxyl group or a 3′-hydroxyl group, to H-phosphonation to convert the 5′-hydroxyl group or the 3′-hydroxyl group into an H-phosphonated form.

### Claim 2 (depends on 1)

The production method according to claim 1, which comprises at least one elongation reaction cycle comprising a step of subjecting a nucleoside or oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of 2′-position, 3′-position, 5′-position and a nucleobase moiety and having a 5′-hydroxyl group or a 3′-hydroxyl group, to H-phosphonation to convert the 5′-hydroxyl group or the 3′-hydroxyl group into an H-phosphonated form.

### Claim 3 (depends on 2)

The production method according to claim 2, wherein the elongation reaction cycle comprises:
a first step including deprotecting a first nucleoside or first oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of 2′-position, 3′-position and a nucleobase moiety, having a 3′-hydroxyl group protected with a basic protecting group or a pseudo solid phase-protecting group, and having a 5′-hydroxyl group protected with a temporary protecting group, to remove the temporary protecting group to form a 5′-hydroxyl group,
a second step including converting the resultant 5′-hydroxyl group into an H-phosphonated form using an H-phosphonate reagent, and
a third step of forming an oligomer of the first nucleoside or first oligonucleotide with a second nucleoside or second oligonucleotide having a 3′-hydroxyl group and having a 5′-hydroxyl group protected with a temporary protecting group, by forming a phosphite diester bond from the 5′-hydroxyl group, now converted to the H-phosphonated form, of the first nucleoside or first oligonucleotide and the 3′-hydroxyl group of the second nucleoside or second oligonucleotide.

### Claim 4 (depends on 3)

The production method according to claim 3, further comprising a fourth step including converting the phosphite diester bond of the oligomer into a phosphodiester bond, a thiophosphodiester bond, a boranophosphodiester bond, an aminophosphodiester bond, a phosphodiester bond protected with a basic protecting group, or a thiophosphodiester bond protected with a basic protecting group.

### Claim 5 (depends on 3)

The production method according to claim 3, further comprising a fourth step including converting the phosphite diester bond of the oligomer into a phosphodiester bond, a thiophosphodiester bond, a boranophosphodiester bond or an aminophosphodiester bond.

### Claim 6 (depends on 4)

The production method according to claim 4, further comprising a fifth step of adding a polar solvent to a reaction mixture obtained from at least one step selected from the group consisting of the first step to the fourth step to form a precipitate, and collecting the precipitate by solid liquid separation.

### Claim 7 (depends on 6)

The production method according to claim 6, wherein the polar solvent is an alcohol solvent with 1 to 6 carbon atoms or a nitrile solvent with 1 to 6 carbon atoms.

### Claim 8 (depends on 3)

The production method according to claim 3, further comprising a sixth step of removing all of the basic protecting group, the temporary protecting group and the pseudo solid phase-protecting group.

### Claim 9 (depends on 3)

The production method according to claim 3, wherein the first nucleoside or the first oligonucleotide has a hydroxyl group protected with a pseudo solid phase-protecting group at 3′-position.

### Claim 10 (depends on 3)

The production method according to claim 3, wherein the third step uses the second nucleoside.

### Claim 11 (depends on 2)

The production method according to claim 2, wherein the elongation reaction cycle comprises:
a seventh step including deprotecting a third nucleoside or third oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of 2′-position, 5′-position and a nucleobase moiety, having a 5′-hydroxyl group protected with a basic protecting group or a pseudo solid phase-protecting group, and having a 3′-hydroxyl group protected with a temporary protecting group, to remove the temporary protecting group to form a 3′-hydroxyl group,
an eighth step including converting the resultant 3′-hydroxyl group into an H-phosphonated form using an H-phosphonate reagent, and
a ninth step of forming an oligomer of the third nucleoside or third oligonucleotide with a fourth nucleoside or fourth oligonucleotide having a 5′-hydroxyl group and having a 3′-hydroxyl group protected with a temporary protecting group, by forming a phosphite diester bond from the 3′-hydroxyl group, now converted to the H-phosphonated form, of the third nucleoside or third oligonucleotide and the 5′-hydroxyl group of the fourth nucleoside or fourth oligonucleotide.

### Claim 12 (depends on 11)

The production method according to claim 11, further comprising a tenth step including converting the phosphite diester bond of the oligomer into a phosphodiester bond, a thiophosphodiester bond, a boranophosphodiester bond, an aminophosphodiester bond, a phosphodiester bond protected with a basic protecting group, or a thiophosphodiester bond protected with a basic protecting group.

### Claim 13 (depends on 11)

The production method according to claim 11, further comprising a tenth step including converting the phosphite diester bond of the oligomer into a phosphodiester bond, a thiophosphodiester bond, a boranophosphodiester bond or an aminophosphodiester bond.

### Claim 14 (depends on 12)

The production method according to claim 12, further comprising an eleventh step of adding a polar solvent to a reaction mixture obtained from any of the seventh step to the tenth step to form a precipitate, and collecting the precipitate by solid liquid separation.

### Claim 15 (depends on 14)

The production method according to claim 14, wherein the polar solvent is an alcohol solvent with 1 to 6 carbon atoms or a nitrile solvent with 1 to 6 carbon atoms.

### Claim 16 (depends on 11)

The production method according to claim 11, further comprising a twelfth step of removing all of the basic protecting group, the temporary protecting group and the pseudo solid phase-protecting group.

### Claim 17 (depends on 11)

The production method according to claim 11, wherein the third nucleoside or the third oligonucleotide has a hydroxyl group protected with a pseudo solid phase-protecting group at 5′-position.

### Claim 18 (depends on 11)

The production method according to claim 11, wherein the ninth step uses the fourth nucleoside.

### Claim 19 (depends on 1)

The production method according to claim 1, wherein the pseudo solid phase-protecting group is represented by the following formula (I):
wherein
* indicates a bond to a group protected by the pseudo solid phase-protecting group,
R1 is a C1-40 alkyl group, a C2-40 alkenyl group or a C2-40 alkynyl group, s is an integer of 1 to 5,
L1 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L2 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L3 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L4 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L5 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group,
L6 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group,
m is 0 or 1, and
when the pseudo solid phase-protecting group is present in the nucleobase moiety and
when m in the pseudo solid phase-protecting group is 0, the number of single bonds represented by L1, L2, L3 and L4 in the pseudo solid phase-protecting group is 0 to 3.

### Claim 20 (depends on 1)

The production method according to claim 1, wherein the pseudo solid phase-protecting group is represented by the following formula (II):
wherein
* indicates a bond to a group protected by the pseudo solid phase-protecting group,
R1 is a C1-40 alkyl group, a C2-40 alkenyl group or a C2-40 alkynyl group, s is an integer of 1 to 5,
L1 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L2 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group) or —O—,
L3 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L4 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group) or —O—, and
when the pseudo solid phase-protecting group is present in the nucleobase moiety, the number of single bonds represented by L1, L2, L3 and L4 in the pseudo solid phase-protecting group is 0 to 3.

### Claim 21 (depends on 3)

The production method according to claim 3, wherein the temporary protecting group is a tert-butyldimethylsilyl group, a 4,4′-dimethoxytrityl group or a levulinyl group.

### Claim 22 (depends on 1)

The production method according to claim 1, wherein the H-phosphonation step uses at least one H-phosphonate reagent selected from the group consisting of phosphorous acid, diphenyl phosphite, phenyl-H-phosphonate triethylammonium salt, p-toluyl-H-phosphonate triethylammonium salt, 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one and phosphorus trichloride.

### Claim 23 (depends on 1)

The production method according to claim 1, wherein the nucleobases present in the first to the fourth nucleosides and the first to the fourth oligonucleotides are each independently at least one selected from the group consisting of 6-aminopurin-9-yl group (adenine residue), 2-amino-6-hydroxypurin-9-yl group (guanine residue), 2-oxo-4-amino-1,2-dihydropyrimidin-1-yl group (cytosine residue), 2-oxo-4-amino-5-methyl-1,2-dihydropyrimidin-1-yl group (5-methylcytosine residue), 2-oxo-4-hydroxy-1,2-dihydropyrimidin-1-yl group (uracil residue) and 2-oxo-4-hydroxy-5-methyl-1,2-dihydropyrimidin-1-yl group (thymine residue).

### Claim 24

A compound represented by the following formula (XI), or a salt thereof:
wherein
n is an integer of 1 or greater,
BaseZ independently at each occurrence is a nucleobase, a nucleobase protected with a basic protecting group, or a nucleobase protected with a pseudo solid phase-protecting group,
XZ independently at each occurrence is a hydrogen atom, a halogen atom, a hydroxyl group, a hydroxyl group protected with a basic protecting group, an organic group bridged to the 4-carbon atom, or a hydroxyl group protected with a pseudo solid phase-protecting group,
Y independently at each occurrence is a hydrogen atom, a hydroxyl group, a hydroxyl group protected with a basic protecting group, a thiol group, a thiol group protected with a basic protecting group, a borohydride group, a mono-C1-6 alkylamino group or a di-C1-6 alkylamino group,
Z is a hydrogen atom, a basic protecting group, a temporary protecting group or a pseudo solid phase-protecting group, and
the compound or salt thereof satisfies at least one of that at least one BaseZ is a nucleobase protected with a pseudo solid phase-protecting group, that at least one XZ is a hydroxyl group protected with a pseudo solid phase-protecting group, and that Z is a pseudo solid phase-protecting group.

### Claim 25 (depends on 24)

The compound or salt thereof according to claim 24, wherein the pseudo solid phase-protecting group is represented by the following formula (II):
wherein
* indicates a bond to a group protected by the pseudo solid phase-protecting group,
R1 is a C1-40 alkyl group, a C2-40 alkenyl group or a C2-40 alkynyl group, s is an integer of 1 to 5,
L1 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L2 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group) or —O—,
L3 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L4 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group) or —O—, and
when the pseudo solid phase-protecting group is present in the nucleobase moiety, the number of single bonds represented by L1, L2, L3 and L4 in the pseudo solid phase-protecting group is 0 to 3.

### Claim 26 (depends on 24)

The compound or salt thereof according to claim 24, which satisfies at least one of that at least one BaseZ in the formula (XI) is a nucleobase protected with a pseudo solid phase-protecting group, and that Z is a pseudo solid phase-protecting group.

### Claim 27 (depends on 24)

The compound or salt thereof according to claim 24, wherein Z in the formula (XI) is a pseudo solid phase-protecting group.

### Claim 28 (depends on 24)

The compound or salt thereof according to claim 24, wherein n in the formula (XI) is 1 to 30.

### Claim 29

A compound represented by the following formula (XII), or a salt thereof:
wherein
n is an integer of 1 or greater,
BaseZ independently at each occurrence is a nucleobase, a nucleobase protected with a basic protecting group, or a nucleobase protected with a pseudo solid phase-protecting group,
XZ independently at each occurrence is a hydrogen atom, a halogen atom, a hydroxyl group, a hydroxyl group protected with a basic protecting group, an organic group bridged to the 4-carbon atom, or a hydroxyl group protected with a pseudo solid phase-protecting group,
Y independently at each occurrence is a hydrogen atom, a hydroxyl group, a hydroxyl group protected with a basic protecting group, a thiol group, a thiol group protected with a basic protecting group, a borohydride group, a mono-C1-6 alkylamino group or a di-C1-6 alkylamino group,
Z is a hydrogen atom, a basic protecting group, a temporary protecting group or a pseudo solid phase-protecting group, and
the compound or salt thereof satisfies at least one of that at least one BaseZ is a nucleobase protected with a pseudo solid phase-protecting group, that at least one XZ is a hydroxyl group protected with a pseudo solid phase-protecting group, and that Z is a pseudo solid phase-protecting group.

### Claim 30 (depends on 29)

The compound or salt thereof according to claim 29, wherein the pseudo solid phase-protecting group is represented by the following formula (II):
wherein
* indicates a bond to a group protected by the pseudo solid phase-protecting group,
R1 is a C1-40 alkyl group, a C2-40 alkenyl group or a C2-40 alkynyl group, s is an integer of 1 to 5,
L1 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L2 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group) or —O—,
L3 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L4 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group) or —O—, and
when the pseudo solid phase-protecting group is present in the nucleobase moiety, the number of single bonds represented by L1, L2, L3 and L4 in the pseudo solid phase-protecting group is 0 to 3.

### Claim 31 (depends on 29)

The compound or salt thereof according to claim 29, which satisfies at least one of that at least one BaseZ in the formula (XII) is a nucleobase protected with a pseudo solid phase-protecting group, and that Z is a pseudo solid phase-protecting group.

### Claim 32 (depends on 29)

The compound or salt thereof according to claim 29, wherein Z in the formula (XII) is a pseudo solid phase-protecting group.

### Claim 33 (depends on 29)

The compound or salt thereof according to claim 29, wherein n in the formula (XII) is 1 to 30.

### Claim 34

A compound represented by the following formula (XIII), or a salt thereof:
wherein
n is an integer of 1 or greater,
BaseZ independently at each occurrence is a nucleobase, a nucleobase protected with a basic protecting group, or a nucleobase protected with a pseudo solid phase-protecting group,
XZ independently at each occurrence is a hydrogen atom, a halogen atom, a hydroxyl group, a hydroxyl group protected with a basic protecting group, an organic group bridged to the 4-carbon atom, or a hydroxyl group protected with a pseudo solid phase-protecting group,
W is a hydrogen atom or a temporary protecting group,
Y independently at each occurrence is a hydrogen atom, a hydroxyl group, a hydroxyl group protected with a basic protecting group, a thiol group, a thiol group protected with a basic protecting group, a borohydride group, a mono-C1-6 alkylamino group or a di-C1-6 alkylamino group,
Z is a hydrogen atom, a basic protecting group, a temporary protecting group or a pseudo solid phase-protecting group,
the compound or salt thereof satisfies at least one of that at least one BaseZ is a nucleobase protected with a pseudo solid phase-protecting group, that at least one XZ is a hydroxyl group protected with a pseudo solid phase-protecting group, and that Z is a pseudo solid phase-protecting group, and
at least one of the pseudo solid phase-protecting groups is represented by the formula (I):
wherein
* indicates a bond to a group protected by the pseudo solid phase-protecting group,
R1 is a C1-40 alkyl group, a C2-40 alkenyl group or a C2-40 alkynyl group, s is an integer of 1 to 5,
L1 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L2 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L3 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L4 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L5 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group,
L6 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group, and
m is 0 or 1 with the proviso that when m is 0, L4 is not a single bond.

### Claim 35

A compound represented by the following formula (XIV), or a salt thereof:
wherein
n is an integer of 1 or greater,
BaseZ independently at each occurrence is a nucleobase, a nucleobase protected with a basic protecting group, or a nucleobase protected with a pseudo solid phase-protecting group,
XZ independently at each occurrence is a hydrogen atom, a halogen atom, a hydroxyl group, a hydroxyl group protected with a basic protecting group, an organic group bridged to the 4-carbon atom, or a hydroxyl group protected with a pseudo solid phase-protecting group,
W is a hydrogen atom or a temporary protecting group,
Y independently at each occurrence is a hydrogen atom, a hydroxyl group, a hydroxyl group protected with a basic protecting group, a thiol group, a thiol group protected with a basic protecting group, a borohydride group, a mono-C1-6 alkylamino group or a di-C1-6 alkylamino group,
Z is a hydrogen atom, a basic protecting group, a temporary protecting group or a pseudo solid phase-protecting group,
the compound or salt thereof satisfies at least one of that at least one BaseZ is a nucleobase protected with a pseudo solid phase-protecting group, that at least one XZ is a hydroxyl group protected with a pseudo solid phase-protecting group, and that Z is a pseudo solid phase-protecting group, and
at least one of the pseudo solid phase-protecting groups is represented by the formula (I):
wherein
* indicates a bond to a group protected by the pseudo solid phase-protecting group,
R1 is a C1-40 alkyl group, a C2-40 alkenyl group or a C2-40 alkynyl group, s is an integer of 1 to 5,
L1 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L2 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L3 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L4 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L5 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group,
L6 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group, and
m is 0 or 1 with the proviso that when m is 0, L4 is not a single bond.

### Claim 36

A pseudo solid phase-protecting group represented by the following formula (I):
wherein
* indicates a bond to at least one selected from the group consisting of 2′-, 3′- and 5′-hydroxyl groups and a nucleobase moiety of a nucleoside or oligonucleotide,
R1 is a C1-40 alkyl group, a C2-40 alkenyl group or a C2-40 alkynyl group, s is an integer of 1 to 5,
L1 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L2 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L3 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L4 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L5 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group,
L6 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group, and
m is 0 or 1 with the proviso that when m is 0, L4 is not a single bond.

### Claim 37

A method for producing a nucleoside or oligonucleotide, comprising reacting a nucleoside or oligonucleotide having:
a hydroxyl group or a protected hydroxyl group independently at 3′-position and 5′-position, and
a hydroxyl group in at least one location selected from the group consisting of 2′-position, 3′-position, 5′-position and a nucleobase moiety, or a hydroxyl or amino group in at least one location of 2′-position and a nucleobase moiety, with
a carboxyl compound represented by the following formula (X-1):
wherein
R1 is a C1-40 alkyl group, a C2-40 alkenyl group or a C2-40 alkynyl group, s is an integer of 1 to 5,
L1 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L2 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L3 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L4 is —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—, or with
an acid halide represented by the following formula (X-2):
wherein X is a halogen atom, and R1, L1, L2, L3 and L4 are the same as defined in the formula (X-1), or with
an alkyl halide compound represented by the following formula (X-3):
wherein X is a halogen atom, R1, L1, L2 and L3 are the same as defined in the formula (X-1),
L4 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L5 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group, and
L6 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group; thereby producing a nucleoside or oligonucleotide having, in at least one location selected from the group consisting of 2′-position, 3′-position, 5′-position and a nucleobase moiety, a pseudo solid phase-protecting group represented by the following formula (I):
wherein * indicates a bond to at least one selected from the group consisting of the 2′-position, the 3′-position, the 5′-position and the nucleobase moiety,
R1 is a C1-40 alkyl group, a C2-40 alkenyl group or a C2-40 alkynyl group, s is an integer of 1 to 5,
L1 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L2 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L3 is a single bond, a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group,
L4 is a single bond, —COO—, —CON(R2)— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —OCO—, —N(R2)CO— (wherein R2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group), —C(O)— or —O—,
L5 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group,
L6 is a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C2-6 alkenyl group or a C2-6 haloalkenyl group, and
m is 0 or 1 with the proviso that when m is 0, L4 is not a single bond.