DK2857412T3 - Method for Oligonucleotide Synthesis Using High-Resolution Liquid Phase Carrier - Google Patents
Method for Oligonucleotide Synthesis Using High-Resolution Liquid Phase Carrier Download PDFInfo
- Publication number
- DK2857412T3 DK2857412T3 DK12877844.6T DK12877844T DK2857412T3 DK 2857412 T3 DK2857412 T3 DK 2857412T3 DK 12877844 T DK12877844 T DK 12877844T DK 2857412 T3 DK2857412 T3 DK 2857412T3
- Authority
- DK
- Denmark
- Prior art keywords
- group
- solution
- nucleoside
- compound
- reaction
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 71
- 238000002515 oligonucleotide synthesis Methods 0.000 title description 15
- 239000007791 liquid phase Substances 0.000 title description 14
- 239000002777 nucleoside Substances 0.000 claims description 72
- -1 nucleoside phosphoramidite compound Chemical class 0.000 claims description 63
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 56
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 50
- 150000001875 compounds Chemical class 0.000 claims description 44
- 125000004432 carbon atom Chemical group C* 0.000 claims description 37
- 108091034117 Oligonucleotide Proteins 0.000 claims description 33
- 125000006239 protecting group Chemical group 0.000 claims description 33
- 239000012454 non-polar solvent Substances 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000002947 alkylene group Chemical group 0.000 claims description 16
- 238000006482 condensation reaction Methods 0.000 claims description 13
- 125000001165 hydrophobic group Chemical group 0.000 claims description 13
- 239000002994 raw material Substances 0.000 claims description 11
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 108020004707 nucleic acids Proteins 0.000 claims description 9
- 150000007523 nucleic acids Chemical class 0.000 claims description 9
- 102000039446 nucleic acids Human genes 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
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- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
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- 238000001308 synthesis method Methods 0.000 description 4
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- AILAQOYFPLQIFN-UHFFFAOYSA-N butyl piperazine-1-carboxylate Chemical compound CCCCOC(=O)N1CCNCC1 AILAQOYFPLQIFN-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- UNXNGGMLCSMSLH-UHFFFAOYSA-N dihydrogen phosphate;triethylazanium Chemical compound OP(O)(O)=O.CCN(CC)CC UNXNGGMLCSMSLH-UHFFFAOYSA-N 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001643 poly(ether ketone) Polymers 0.000 description 1
- 229920006122 polyamide resin Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/02—Phosphorylation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/02—Phosphorylation
- C07H1/04—Introducing polyphosphoric acid radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/JP2012/063921 WO2013179412A1 (ja) | 2012-05-30 | 2012-05-30 | 高分散性液相支持体を用いたオリゴヌクレオチド合成法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2857412T3 true DK2857412T3 (en) | 2017-04-03 |
Family
ID=49672666
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK12877844.6T DK2857412T3 (en) | 2012-05-30 | 2012-05-30 | Method for Oligonucleotide Synthesis Using High-Resolution Liquid Phase Carrier |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US9284344B2 (enExample) |
| EP (1) | EP2857412B1 (enExample) |
| DK (1) | DK2857412T3 (enExample) |
| IL (1) | IL235978B (enExample) |
| IN (1) | IN2014DN10144A (enExample) |
| SG (1) | SG11201407967TA (enExample) |
| WO (1) | WO2013179412A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
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| BRPI0923225A2 (pt) | 2008-12-02 | 2016-10-04 | Chiralgen Ltd | metodo para sintese de acidos nucleicos modificados no atomo de fosforo |
| EP2451461A4 (en) | 2009-07-06 | 2013-05-29 | Ontorii Inc | NOVEL NUCLEIC ACID PRODRUGS AND METHOD OF USE THEREOF |
| DK2620428T3 (da) | 2010-09-24 | 2019-07-01 | Wave Life Sciences Ltd | Asymmetrisk hjælpegruppe |
| CN107365339A (zh) | 2011-07-19 | 2017-11-21 | 波涛生命科学有限公司 | 合成官能化核酸的方法 |
| US8846885B2 (en) | 2012-02-17 | 2014-09-30 | Ajinomoto Co., Inc. | Oligonucleotide with protected base |
| IN2014DN06768A (enExample) * | 2012-02-17 | 2015-05-22 | Ajinomoto Kk | |
| DK2872147T3 (da) | 2012-07-13 | 2023-02-20 | Wave Life Sciences Ltd | Fremgangsmåde til fremstilling af kirale oligonukleotider |
| SG11201500243WA (en) | 2012-07-13 | 2015-04-29 | Shin Nippon Biomedical Lab Ltd | Chiral nucleic acid adjuvant |
| WO2014010250A1 (en) | 2012-07-13 | 2014-01-16 | Chiralgen, Ltd. | Asymmetric auxiliary group |
| EP3095461A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
| WO2015108046A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 抗アレルギー作用を有するキラル核酸アジュバンド及び抗アレルギー剤 |
| EP3095459A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having antitumor effect and antitumor agent |
| EP3094728B1 (en) | 2014-01-16 | 2022-03-09 | Wave Life Sciences Ltd. | Chiral design |
| CN108350018A (zh) | 2015-11-17 | 2018-07-31 | 日产化学工业株式会社 | 寡核苷酸的制造方法 |
| EP3398955B1 (en) * | 2015-12-16 | 2026-06-03 | Ajinomoto Co., Inc. | Oligonucleotide production method, and nucleoside, nucleotide, or oligonucleotide |
| JPWO2017111137A1 (ja) | 2015-12-22 | 2018-10-18 | 味の素株式会社 | オリゴヌクレオチドの製造方法 |
| CN113423715A (zh) | 2019-02-15 | 2021-09-21 | 味之素株式会社 | 寡核苷酸的制造方法 |
| CN113490679A (zh) | 2019-02-28 | 2021-10-08 | 富士胶片株式会社 | 肽化合物的制造方法、保护基形成用试药及芳香族杂环化合物 |
| KR102668387B1 (ko) | 2019-02-28 | 2024-05-22 | 후지필름 가부시키가이샤 | 펩타이드 화합물의 제조 방법, 보호기 형성용 시약, 및 축합 다환 방향족 탄화 수소 화합물 |
| EP3950698A4 (en) | 2019-03-28 | 2023-01-25 | Ajinomoto Co., Inc. | METHOD OF PREPARING AN OLIGONUCLEOTIDE WITH PHOSPHOROTHIOATE SITE |
| CN114206897B (zh) * | 2019-05-08 | 2024-09-20 | 比奥根Ma公司 | 寡核苷酸的汇聚液相合成 |
| WO2021039935A1 (ja) * | 2019-08-29 | 2021-03-04 | 富士フイルム株式会社 | 核酸化合物の製造方法、及び、核酸化合物 |
| US12649761B2 (en) | 2020-03-31 | 2026-06-09 | Janssen Biopharma, Inc. | Synthesis of oligonucleotides and related compounds |
| FR3111896A1 (fr) | 2020-06-24 | 2021-12-31 | Strainchem | Procédés de synthèses en solution de macromolécules à partir d’unités de dérivés de glucides |
| CN113583069B (zh) * | 2021-09-09 | 2023-06-06 | 北京大学 | 核苷磷脂类化合物及其化学合成方法和在核酸递送中的应用 |
| WO2024083746A1 (en) | 2022-10-17 | 2024-04-25 | Bachem Holding Ag | Method and composition for oligonucleotide synthesis |
| WO2024137756A1 (en) * | 2022-12-23 | 2024-06-27 | Hongene Biotech Corporation | Compounds and methods for liquid phase oligonucleotide synthesis |
| EP4678626A1 (en) | 2023-03-06 | 2026-01-14 | Spera Pharma, Inc. | Long-chain alkenyloxy-substituted benzoyl derivative and oligonucleotide synthesis method using same |
| EP4695265A1 (en) | 2023-10-16 | 2026-02-18 | Bachem Holding AG | Method and composition for oligonucleotide synthesis |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7094943B2 (en) | 1998-04-27 | 2006-08-22 | Hubert Köster | Solution phase biopolymer synthesis |
| JP2003002895A (ja) | 2001-05-30 | 2003-01-08 | Tokyo Inst Of Technol | 核酸の合成法 |
| JP4963665B2 (ja) | 2007-11-27 | 2012-06-27 | 株式会社ミツバ | 扁平型コミュテータ及びその製造方法 |
| JP5548852B2 (ja) * | 2009-05-29 | 2014-07-16 | 国立大学法人東京農工大学 | 疎水性基結合ヌクレオシド、疎水性基結合ヌクレオシド溶液、及び疎水性基結合オリゴヌクレオチド合成方法 |
| US9029528B2 (en) | 2011-05-17 | 2015-05-12 | Ajinomoto Co., Inc. | Solution-based method of making oligonucleotides via phosphoramidite coupling |
| IN2014DN06768A (enExample) | 2012-02-17 | 2015-05-22 | Ajinomoto Kk |
-
2012
- 2012-05-30 WO PCT/JP2012/063921 patent/WO2013179412A1/ja not_active Ceased
- 2012-05-30 DK DK12877844.6T patent/DK2857412T3/en active
- 2012-05-30 EP EP12877844.6A patent/EP2857412B1/en active Active
- 2012-05-30 IN IN10144DEN2014 patent/IN2014DN10144A/en unknown
- 2012-05-30 SG SG11201407967TA patent/SG11201407967TA/en unknown
- 2012-05-30 US US14/404,562 patent/US9284344B2/en active Active
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2014
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Also Published As
| Publication number | Publication date |
|---|---|
| US20150112053A1 (en) | 2015-04-23 |
| SG11201407967TA (en) | 2015-01-29 |
| EP2857412A1 (en) | 2015-04-08 |
| EP2857412B1 (en) | 2017-01-11 |
| WO2013179412A1 (ja) | 2013-12-05 |
| IL235978A0 (en) | 2015-02-01 |
| EP2857412A4 (en) | 2015-10-21 |
| IN2014DN10144A (enExample) | 2015-08-21 |
| US9284344B2 (en) | 2016-03-15 |
| IL235978B (en) | 2018-02-28 |
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