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 (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010064146A2 (en) | 2008-12-02 | 2010-06-10 | Chiralgen, Ltd. | Method for the synthesis of phosphorus atom modified nucleic acids |
| CA2767253A1 (en) | 2009-07-06 | 2011-01-13 | Ontorii, Inc. | Novel nucleic acid prodrugs and methods of use thereof |
| WO2012039448A1 (ja) | 2010-09-24 | 2012-03-29 | 株式会社キラルジェン | 不斉補助基 |
| CN103796657B (zh) | 2011-07-19 | 2017-07-11 | 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 |
| JP6237237B2 (ja) * | 2012-02-17 | 2017-11-29 | 味の素株式会社 | 塩基部保護オリゴヌクレオチド |
| CA2879066C (en) | 2012-07-13 | 2019-08-13 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
| WO2014010250A1 (en) | 2012-07-13 | 2014-01-16 | Chiralgen, Ltd. | Asymmetric auxiliary group |
| JP6453212B2 (ja) | 2012-07-13 | 2019-01-16 | ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． | キラル制御 |
| JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| JPWO2015108046A1 (ja) | 2014-01-15 | 2017-03-23 | 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 |
| WO2015108047A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
| KR20230152178A (ko) | 2014-01-16 | 2023-11-02 | 웨이브 라이프 사이언시스 리미티드 | 키랄 디자인 |
| TWI729028B (zh) * | 2015-11-17 | 2021-06-01 | 日商日產化學工業股份有限公司 | 寡核苷酸的製造方法 |
| JP7027889B2 (ja) * | 2015-12-16 | 2022-03-02 | 味の素株式会社 | オリゴヌクレオチドの製造方法、およびヌクレオシド、ヌクレオチドまたはオリゴヌクレオチド |
| WO2017111137A1 (ja) * | 2015-12-22 | 2017-06-29 | 味の素株式会社 | オリゴヌクレオチドの製造方法 |
| WO2020166705A1 (ja) | 2019-02-15 | 2020-08-20 | 味の素株式会社 | オリゴヌクレオチドの製造方法 |
| WO2020175472A1 (ja) | 2019-02-28 | 2020-09-03 | 富士フイルム株式会社 | ペプチド化合物の製造方法、保護基形成用試薬、及び、縮合多環芳香族炭化水素化合物 |
| WO2020175473A1 (ja) | 2019-02-28 | 2020-09-03 | 富士フイルム株式会社 | ペプチド化合物の製造方法、保護基形成用試薬、及び、芳香族複素環化合物 |
| EP3950698A4 (en) * | 2019-03-28 | 2023-01-25 | Ajinomoto Co., Inc. | METHOD OF PREPARING AN OLIGONUCLEOTIDE WITH PHOSPHOROTHIOATE SITE |
| MA55891A (fr) | 2019-05-08 | 2022-03-16 | Ajinomoto Kk | Synthèses en phase liquide convergente d'oligonucléotides |
| 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 |
| WO2021198883A1 (en) | 2020-03-31 | 2021-10-07 | 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 |
| WO2025082632A1 (en) | 2023-10-16 | 2025-04-24 | 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 |
| WO2012157723A1 (ja) | 2011-05-17 | 2012-11-22 | 味の素株式会社 | オリゴヌクレオチドの製造方法 |
| JP6237237B2 (ja) * | 2012-02-17 | 2017-11-29 | 味の素株式会社 | 塩基部保護オリゴヌクレオチド |
-
2012
- 2012-05-30 US US14/404,562 patent/US9284344B2/en active Active
- 2012-05-30 SG SG11201407967TA patent/SG11201407967TA/en unknown
- 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 IN IN10144DEN2014 patent/IN2014DN10144A/en unknown
- 2012-05-30 EP EP12877844.6A patent/EP2857412B1/en active Active
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2014
- 2014-11-27 IL IL235978A patent/IL235978B/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| IL235978B (en) | 2018-02-28 |
| US20150112053A1 (en) | 2015-04-23 |
| EP2857412A4 (en) | 2015-10-21 |
| US9284344B2 (en) | 2016-03-15 |
| SG11201407967TA (en) | 2015-01-29 |
| WO2013179412A1 (ja) | 2013-12-05 |
| EP2857412B1 (en) | 2017-01-11 |
| IN2014DN10144A (enExample) | 2015-08-21 |
| EP2857412A1 (en) | 2015-04-08 |
| IL235978A0 (en) | 2015-02-01 |
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