NO309482B1 - Fremgangsmåte for syntese av mer enn ett oligonukleotid samt forbindelse og anvendelse derav - Google Patents

Fremgangsmåte for syntese av mer enn ett oligonukleotid samt forbindelse og anvendelse derav Download PDF

Info

Publication number: NO309482B1
Authority: NO; Norway
Prior art keywords: formula; group; oligonucleotide; optionally substituted; compound according
Prior art date: 1992-04-03

Application number

NO943660A

Other languages

English (en)

Norwegian (no)

Other versions

NO943660D0 (no

NO943660L (no

Inventor

Michael Joseph Mclean

David Holland

Andrew John Garman

Robert Charles Sheppard

Original Assignee

Zeneca Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-04-03

Filing date

1994-09-30

Publication date

2001-02-05

1994-09-30 Application filed by Zeneca Ltd filed Critical Zeneca Ltd

1994-09-30 Publication of NO943660D0 publication Critical patent/NO943660D0/no

1994-09-30 Publication of NO943660L publication Critical patent/NO943660L/no

2001-02-05 Publication of NO309482B1 publication Critical patent/NO309482B1/no

Links

108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 99
150000001875 compounds Chemical class 0.000 title claims abstract description 60
238000000034 method Methods 0.000 title claims abstract description 36
230000015572 biosynthetic process Effects 0.000 title claims abstract description 19
238000003786 synthesis reaction Methods 0.000 title claims abstract description 17
230000008569 process Effects 0.000 title description 2
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims abstract description 46
125000005647 linker group Chemical group 0.000 claims abstract description 42
239000007787 solid Substances 0.000 claims abstract description 21
238000003776 cleavage reaction Methods 0.000 claims description 14
-1 dimethoxytrityl Chemical group 0.000 claims description 14
230000007017 scission Effects 0.000 claims description 14
125000006239 protecting group Chemical group 0.000 claims description 13
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
150000008300 phosphoramidites Chemical class 0.000 claims description 12
238000004519 manufacturing process Methods 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 9
229910019142 PO4 Inorganic materials 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
239000010452 phosphate Substances 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
238000002515 oligonucleotide synthesis Methods 0.000 claims description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 5
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
125000004430 oxygen atom Chemical group O* 0.000 claims description 4
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
125000006850 spacer group Chemical group 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000003368 amide group Chemical group 0.000 claims description 2
125000003710 aryl alkyl group Chemical group 0.000 claims description 2
125000003118 aryl group Chemical group 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
229910052757 nitrogen Inorganic materials 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 2
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 2
SXADIBFZNXBEGI-UHFFFAOYSA-N phosphoramidous acid Chemical group NP(O)O SXADIBFZNXBEGI-UHFFFAOYSA-N 0.000 claims description 2
125000003386 piperidinyl group Chemical class 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
150000003568 thioethers Chemical class 0.000 claims description 2
150000003235 pyrrolidines Chemical class 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 32
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
239000003153 chemical reaction reagent Substances 0.000 description 21
239000000047 product Substances 0.000 description 21
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 18
239000002904 solvent Substances 0.000 description 18
238000002360 preparation method Methods 0.000 description 16
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 15
238000010828 elution Methods 0.000 description 13
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
239000000377 silicon dioxide Substances 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 11
239000002243 precursor Substances 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
239000002585 base Substances 0.000 description 10
239000000203 mixture Substances 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
239000011521 glass Substances 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
239000002773 nucleotide Substances 0.000 description 8
125000003729 nucleotide group Chemical group 0.000 description 8
229940124276 oligodeoxyribonucleotide Drugs 0.000 description 7
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
229910052786 argon Inorganic materials 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
230000006820 DNA synthesis Effects 0.000 description 5
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230000014759 maintenance of location Effects 0.000 description 5
239000007858 starting material Substances 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
235000011114 ammonium hydroxide Nutrition 0.000 description 4
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238000004587 chromatography analysis Methods 0.000 description 4
238000010549 co-Evaporation Methods 0.000 description 4
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
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UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
239000002777 nucleoside Substances 0.000 description 4
238000002390 rotary evaporation Methods 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
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125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 3
229960000549 4-dimethylaminophenol Drugs 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
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IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 3
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230000008020 evaporation Effects 0.000 description 3
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UBTJZUKVKGZHAD-UHFFFAOYSA-N 1-[5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OCC1C(O)CC(N2C(NC(=O)C(C)=C2)=O)O1 UBTJZUKVKGZHAD-UHFFFAOYSA-N 0.000 description 2
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NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
YLMXBNACRIGGFX-UHFFFAOYSA-N C=1[C-]=NNN=1 Chemical compound C=1[C-]=NNN=1 YLMXBNACRIGGFX-UHFFFAOYSA-N 0.000 description 1
CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
239000005909 Kieselgur Substances 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
108091028664 Ribonucleotide Proteins 0.000 description 1
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
108700005078 Synthetic Genes Proteins 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000003513 alkali Substances 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
238000013459 approach Methods 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000010959 commercial synthesis reaction Methods 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
210000002808 connective tissue Anatomy 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
238000007360 debenzoylation reaction Methods 0.000 description 1
VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 description 1
238000006642 detritylation reaction Methods 0.000 description 1
JUJPMEAAXFYJOI-UHFFFAOYSA-N dichloromethane;n,n-diethylethanamine;hexane Chemical compound ClCCl.CCCCCC.CCN(CC)CC JUJPMEAAXFYJOI-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
125000001183 hydrocarbyl group Chemical group 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
229920000592 inorganic polymer Polymers 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
239000000463 material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
RMQXDNUKLIDXOS-UHFFFAOYSA-N n-[9-[5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-6-oxo-3h-purin-2-yl]-2-methylpropanamide Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)(C=1C=CC=CC=1)OCC1C(O)CC(N2C3=C(C(N=C(NC(=O)C(C)C)N3)=O)N=C2)O1 RMQXDNUKLIDXOS-UHFFFAOYSA-N 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
150000008301 phosphite esters Chemical class 0.000 description 1
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
229920002939 poly(N,N-dimethylacrylamides) Polymers 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
239000002336 ribonucleotide Substances 0.000 description 1
125000002652 ribonucleotide group Chemical group 0.000 description 1
125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
239000000523 sample Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
229940113082 thymine Drugs 0.000 description 1
238000012546 transfer Methods 0.000 description 1
229940035893 uracil Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Biotechnology (AREA)
Genetics & Genomics (AREA)
Saccharide Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

NO943660A 1992-04-03 1994-09-30 Fremgangsmåte for syntese av mer enn ett oligonukleotid samt forbindelse og anvendelse derav NO309482B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB929207381A GB9207381D0 (en)	1992-04-03	1992-04-03	Synthesis of oligonucleotides
PCT/GB1993/000694 WO1993020092A1 (en)	1992-04-03	1993-04-02	Synthesis of oligonucleotides

Publications (3)

Publication Number	Publication Date
NO943660D0 NO943660D0 (no)	1994-09-30
NO943660L NO943660L (no)	1994-09-30
NO309482B1 true NO309482B1 (no)	2001-02-05

Family

ID=10713445

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO943660A NO309482B1 (no)	1992-04-03	1994-09-30	Fremgangsmåte for syntese av mer enn ett oligonukleotid samt forbindelse og anvendelse derav

Country Status (12)

Country	Link
US (2)	US5393877A (de)
EP (1)	EP0633891B1 (de)
JP (1)	JPH07505290A (de)
AT (1)	ATE148129T1 (de)
AU (1)	AU674847B2 (de)
CA (1)	CA2131994A1 (de)
DE (1)	DE69307689T2 (de)
FI (1)	FI109702B (de)
GB (1)	GB9207381D0 (de)
NO (1)	NO309482B1 (de)
RU (1)	RU94042224A (de)
WO (1)	WO1993020092A1 (de)

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JP4503828B2 (ja) *	1998-02-11	2010-07-14	ユニバーシティーオブヒューストン	光生成試薬を用いる化学反応および生化学反応のための方法および装置
US7094943B2 (en)	1998-04-27	2006-08-22	Hubert Köster	Solution phase biopolymer synthesis
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US6451998B1 (en)	1999-10-18	2002-09-17	Agilent Technologies, Inc.	Capping and de-capping during oligonucleotide synthesis
WO2002020541A2 (en) *	2000-09-05	2002-03-14	University Technologies International Inc.	Process for producing multiple oligonucleotides on a solid support
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US7635571B2 (en) *	2000-12-07	2009-12-22	Siemens Healthcare Diagnostics Products Gmbh	Amplified signal in binding assays
US7211654B2 (en) *	2001-03-14	2007-05-01	Regents Of The University Of Michigan	Linkers and co-coupling agents for optimization of oligonucleotide synthesis and purification on solid supports
WO2003062452A2 (en) *	2002-01-23	2003-07-31	Proligo, Llc	Methods for the integrated synthesis and purification of oligonucleotides
US6971790B2 (en) *	2002-10-11	2005-12-06	Welch Allyn, Inc.	Thermometry probe calibration method
US7615629B2 (en) *	2002-12-31	2009-11-10	Sigma-Aldrich Co.	Methods and compositions for the tandem synthesis of two or more oligonucleotides on the same solid support
WO2005000859A2 (en) *	2003-04-14	2005-01-06	University Of Houston	Novel reagent compounds and methods of making and using the same
CA2589935A1 (en)	2004-12-09	2006-06-15	Regents Of The University Of Minnesota	Nucleosides with antiviral and anticancer activity
US20060286572A1 (en) *	2005-05-16	2006-12-21	Kohne David E	Method for producing chemically synthesized and in vitro enzymatically synthesized nucleic acid oligomers
US8053191B2 (en)	2006-08-31	2011-11-08	Westend Asset Clearinghouse Company, Llc	Iterative nucleic acid assembly using activation of vector-encoded traits
US20090036660A1 (en) *	2007-07-31	2009-02-05	Joel Myerson	Methods and compositions for generating mixtures of nucleic acid molecules
US20090075840A1 (en) *	2007-09-18	2009-03-19	Joel Myerson	Methods And Compositions For Generating Mixtures Of Nucleic Acid Molecules
US8808986B2 (en)	2008-08-27	2014-08-19	Gen9, Inc.	Methods and devices for high fidelity polynucleotide synthesis
US10022454B2 (en)	2008-09-23	2018-07-17	Liposciences, Llc	Functionalized phosphorodiamites for therapeutic oligonucleotide synthesis
EP3067359A1 (de) *	2008-09-23	2016-09-14	Scott G. Petersen	Selbstfreisetzende biolabile phosphatgeschützte pro-oligos für therapeutika auf oligonukleotidbasis und vermittlung von rna-interferenz
US20120071358A1 (en) *	2008-12-04	2012-03-22	Xiaochuan Zhou	Fluidic devices and methods for multiplex chemical and biochemical reactions
KR101141544B1 (ko)	2009-03-13	2012-05-03	한국과학기술원	에스아이알엔에이 다중 접합체 및 이의 제조방법
US10207240B2 (en)	2009-11-03	2019-02-19	Gen9, Inc.	Methods and microfluidic devices for the manipulation of droplets in high fidelity polynucleotide assembly
US9216414B2 (en)	2009-11-25	2015-12-22	Gen9, Inc.	Microfluidic devices and methods for gene synthesis
US9217144B2 (en)	2010-01-07	2015-12-22	Gen9, Inc.	Assembly of high fidelity polynucleotides
US9295965B2 (en)	2010-11-12	2016-03-29	Gen9, Inc.	Methods and devices for nucleic acid synthesis
US10457935B2 (en)	2010-11-12	2019-10-29	Gen9, Inc.	Protein arrays and methods of using and making the same
US9752176B2 (en)	2011-06-15	2017-09-05	Ginkgo Bioworks, Inc.	Methods for preparative in vitro cloning
ES2737957T3 (es)	2011-08-26	2020-01-17	Gen9 Inc	Composiciones y métodos para el ensamblaje de alta fidelidad de ácidos nucleicos
EP3604555B1 (de)	2011-10-14	2024-12-25	President and Fellows of Harvard College	Sequenzierung durch strukturanordnung
US10202628B2 (en)	2012-02-17	2019-02-12	President And Fellows Of Harvard College	Assembly of nucleic acid sequences in emulsions
US9150853B2 (en)	2012-03-21	2015-10-06	Gen9, Inc.	Methods for screening proteins using DNA encoded chemical libraries as templates for enzyme catalysis
EP2841601B1 (de)	2012-04-24	2019-03-06	Gen9, Inc.	Verfahren zum sortieren von nukleinsäuren und zur multiplexierten, vorbereitenden in-vitro-klonung
US9914967B2 (en)	2012-06-05	2018-03-13	President And Fellows Of Harvard College	Spatial sequencing of nucleic acids using DNA origami probes
CA2877823A1 (en)	2012-06-25	2014-01-03	Gen9, Inc.	Methods for nucleic acid assembly and high throughput sequencing
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GB9021625D0 (en)	1990-10-04	1990-11-21	Ici Plc	Synthesis of oligonucleotides
GB9207381D0 (en) *	1992-04-03	1992-05-13	Ici Plc	Synthesis of oligonucleotides

1992
- 1992-04-03 GB GB929207381A patent/GB9207381D0/en active Pending
1993
- 1993-04-02 RU RU94042224/04A patent/RU94042224A/ru unknown
- 1993-04-02 WO PCT/GB1993/000694 patent/WO1993020092A1/en not_active Ceased
- 1993-04-02 AU AU40424/93A patent/AU674847B2/en not_active Ceased
- 1993-04-02 CA CA002131994A patent/CA2131994A1/en not_active Abandoned
- 1993-04-02 JP JP5517255A patent/JPH07505290A/ja active Pending
- 1993-04-02 EP EP93911532A patent/EP0633891B1/de not_active Expired - Lifetime
- 1993-04-02 AT AT93911532T patent/ATE148129T1/de not_active IP Right Cessation
- 1993-04-02 DE DE69307689T patent/DE69307689T2/de not_active Expired - Fee Related
- 1993-04-05 US US08/041,599 patent/US5393877A/en not_active Expired - Fee Related
1994
- 1994-09-30 NO NO943660A patent/NO309482B1/no not_active IP Right Cessation
- 1994-09-30 FI FI944568A patent/FI109702B/fi not_active IP Right Cessation
- 1994-11-07 US US08/337,025 patent/US5552535A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
FI944568A0 (fi)	1994-09-30
AU674847B2 (en)	1997-01-16
EP0633891A1 (de)	1995-01-18
RU94042224A (ru)	1996-07-20
JPH07505290A (ja)	1995-06-15
ATE148129T1 (de)	1997-02-15
US5552535A (en)	1996-09-03
DE69307689D1 (de)	1997-03-06
GB9207381D0 (en)	1992-05-13
AU4042493A (en)	1993-11-08
DE69307689T2 (de)	1997-05-15
FI944568L (fi)	1994-09-30
WO1993020092A1 (en)	1993-10-14
CA2131994A1 (en)	1993-10-14
US5393877A (en)	1995-02-28
FI109702B (fi)	2002-09-30
NO943660D0 (no)	1994-09-30
NO943660L (no)	1994-09-30
EP0633891B1 (de)	1997-01-22

Legal Events

Date	Code	Title	Description
2004-12-27	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
EP0633891B1 (de)	1997-01-22	Oligonukleotide synthese
AU777049B2 (en)	2004-09-30	Xylo-LNA analogues
US5512668A (en)	1996-04-30	Solid phase oligonucleotide synthesis using phospholane intermediates
US5614622A (en)	1997-03-25	5-pentenoyl moiety as a nucleoside-amino protecting group, 4-pentenoyl-protected nucleotide synthons, and related oligonucleotide syntheses
KR101032008B1 (ko)	2011-05-02	폴리뉴클레오티드 표지 시약
EP0219342B1 (de)	1994-03-16	Verfahren und Reagenzien für die In-vitro-Synthese von Oligonukleotiden
AU776362B2 (en)	2004-09-09	L-ribo-LNA analogues
US6117992A (en)	2000-09-12	Reagents and process for synthesis of oligonucleotides containing phosphorodithioate internucleoside linkages
US5359052A (en)	1994-10-25	Chalcophospholanes useful in the synthesis of oligonucleoside phosphorothioates, phosphorodithioates and related selenates
US5955599A (en)	1999-09-21	Process for making oligonucleotides containing o- and s- methylphosphotriester internucleoside linkages
US5869696A (en)	1999-02-09	Universal solid supports and methods for their use
HUT64555A (en)	1994-01-28	A method for linking nucleosides with syloxane bridge
WO1998039349A1 (en)	1998-09-11	Protecting group for synthesizing oligonucleotide analogs
US5623068A (en)	1997-04-22	Synthesis of DNA using substituted phenylacetyl-protected nucleotides
AU665174B2 (en)	1995-12-21	Synthesis of oligonucleotides
US5859234A (en)	1999-01-12	2'-O-methyl cytidine monomer useful in oligonucleotide synthesis
JPH09503494A (ja)	1997-04-08	カーバメートヌクレオシド間結合を有するビルディングブロックおよびそれから誘導される新規なオリゴヌクレオチド
CA2118153A1 (en)	1995-04-21	Use of nucleosides and nucleoside derivatives provided with enzymatically cleavable protecting groups in the synthesis of oligonucleotides
Iyer et al.	1997	N-pent-4-enoyl (PNT) group as a universal nucleobase protector: Applications in the rapid and facile synthesis of oligonucleotides, analogs, and conjugates
CA2599259A1 (en)	2006-09-14	Synthesis of oligonucleotides
US6509459B1 (en)	2003-01-21	Base protecting groups and rapid process for oligonucleotide synthesis
US5726301A (en)	1998-03-10	CAC H-phosphonate and its use in the synthesis of oligonucleotides