DE3332068A1 - Verfahren zur herstellung von nukleosidalkyl-, aralkyl- und arylphosphoniten und -phosphonaten - Google Patents
Verfahren zur herstellung von nukleosidalkyl-, aralkyl- und arylphosphoniten und -phosphonatenInfo
- Publication number
- DE3332068A1 DE3332068A1 DE19833332068 DE3332068A DE3332068A1 DE 3332068 A1 DE3332068 A1 DE 3332068A1 DE 19833332068 DE19833332068 DE 19833332068 DE 3332068 A DE3332068 A DE 3332068A DE 3332068 A1 DE3332068 A1 DE 3332068A1
- Authority
- DE
- Germany
- Prior art keywords
- general formula
- denotes
- see diagramm
- given above
- group
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- 239000002777 nucleoside Substances 0.000 claims abstract description 17
- 239000000460 chlorine Chemical group 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 239000011669 selenium Substances 0.000 claims abstract description 12
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims abstract description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 10
- 229910052711 selenium Inorganic materials 0.000 claims abstract description 10
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 9
- 150000003833 nucleoside derivatives Chemical class 0.000 claims abstract description 9
- 125000006239 protecting group Chemical group 0.000 claims abstract description 9
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
- 239000011593 sulfur Substances 0.000 claims abstract description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 6
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 230000008569 process Effects 0.000 claims abstract description 5
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 4
- 239000005549 deoxyribonucleoside Substances 0.000 claims abstract description 4
- 239000011737 fluorine Substances 0.000 claims abstract description 4
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 4
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 4
- 230000001588 bifunctional effect Effects 0.000 claims description 4
- 125000003835 nucleoside group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 238000005954 phosphonylation reaction Methods 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 abstract 2
- -1 aryl phosphonites Chemical class 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- XRBCRPZXSCBRTK-UHFFFAOYSA-N phosphonous acid Chemical compound OPO XRBCRPZXSCBRTK-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 239000013256 coordination polymer Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- CDPKWOKGVUHZFR-UHFFFAOYSA-N dichloro(methyl)phosphane Chemical compound CP(Cl)Cl CDPKWOKGVUHZFR-UHFFFAOYSA-N 0.000 description 2
- WFPZPJSADLPSON-UHFFFAOYSA-N dinitrogen tetraoxide Chemical compound [O-][N+](=O)[N+]([O-])=O WFPZPJSADLPSON-UHFFFAOYSA-N 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 2
- SCLFRABIDYGTAZ-UHFFFAOYSA-N methylphosphonic acid dichloride Chemical compound CP(Cl)(Cl)=O SCLFRABIDYGTAZ-UHFFFAOYSA-N 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 150000003536 tetrazoles Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- LKPFWCPZERQLFI-UHFFFAOYSA-N 2,4,6-trimethylpyridine;hydrochloride Chemical compound Cl.CC1=CC(C)=NC(C)=C1 LKPFWCPZERQLFI-UHFFFAOYSA-N 0.000 description 1
- 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 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- LWNLXVXSCCLRRZ-UHFFFAOYSA-N dichlorophosphane Chemical compound ClPCl LWNLXVXSCCLRRZ-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- 150000003008 phosphonic acid esters Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 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
- 238000005809 transesterification reaction Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 125000002223 uridyl group Chemical group 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- 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
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/48—Phosphonous acids [RP(OH)2] including [RHP(=O)(OH)]; Thiophosphonous acids including [RP(SH)2], [RHP(=S)(SH)]; Derivatives thereof
- C07F9/4883—Amides or esteramides thereof, e.g. RP(NR'2)2 or RP(XR')(NR''2) (X = O, S)
-
- 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
-
- 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)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Silicon Polymers (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Priority Applications (17)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19833332068 DE3332068A1 (de) | 1983-09-06 | 1983-09-06 | Verfahren zur herstellung von nukleosidalkyl-, aralkyl- und arylphosphoniten und -phosphonaten |
| EP84110314A EP0136543B1 (de) | 1983-09-06 | 1984-08-30 | Verfahren zur Herstellung von Nukleosidalkyl-, -aralkyl- und -arylphosphoniten und -phosphonaten |
| AT84110314T ATE38839T1 (de) | 1983-09-06 | 1984-08-30 | Verfahren zur herstellung von nukleosidalkyl-, - aralkyl- und -arylphosphoniten und -phosphonaten. |
| DE8484110314T DE3475307D1 (en) | 1983-09-06 | 1984-08-30 | Method for the preparation of nucleosidealkyl, aralkyl and aryl phosphonites and phosphonates |
| PT79172A PT79172B (de) | 1983-09-06 | 1984-09-04 | Verfahren zur herstellung von nukleasidalkyl-aralkyl- und -aryl-phosphoniten und phosphonaten |
| ES535627A ES8505384A1 (es) | 1983-09-06 | 1984-09-04 | Procedimiento para preparar desoxirribonucleosidofosfonatos |
| GR80287A GR80287B (en) | 1983-09-06 | 1984-09-04 | Method for the preparation of nucleosidalkyl-aralkyl-,-arylphosphonites and -phosphonates |
| JP59184717A JPS6072899A (ja) | 1983-09-06 | 1984-09-05 | ヌクレオシドアルキル‐、アルアルキル‐およびアリール‐ホスホナイトおよび‐ホスホネートの製造方法 |
| AU32756/84A AU570266B2 (en) | 1983-09-06 | 1984-09-05 | Preparation of phosphorus-containing nucleoside derivatives |
| CA000462469A CA1235079A (en) | 1983-09-06 | 1984-09-05 | Process for the preparation of nucleoside alkyl-, aralkyl- and aryl-phosphonites and -phosphonates |
| DK424784A DK162895C (da) | 1983-09-06 | 1984-09-05 | Fremgangsmaade til fremstilling af desoxyribonucleosidphosphonater |
| IE2268/84A IE57904B1 (en) | 1983-09-06 | 1984-09-05 | Process for the preparation of nucleoside alkyl-,aralkyl-and aryl-phosphonites and-phosphonates |
| US07/139,112 US5166330A (en) | 1983-09-06 | 1987-12-28 | Process for the preparation of nucleoside alkyl-aralkyl- and aryl-phosphonites and -phosphonates |
| AU11384/88A AU601257B2 (en) | 1983-09-06 | 1988-02-08 | 5'-protected nucleoside phosphonites and process for their preparation |
| DK131691A DK167359B1 (da) | 1983-09-06 | 1991-07-05 | Nucleosidphosphoniter |
| DK131591A DK166585C (da) | 1983-09-06 | 1991-07-05 | Desoxyribonucleosidthio- og -selenphosphonater |
| JP4307481A JPH0662662B2 (ja) | 1983-09-06 | 1992-11-18 | ヌクレオシドアルキル−、アルアルキル−およびアリール−ホスホナイトおよびその製造方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19833332068 DE3332068A1 (de) | 1983-09-06 | 1983-09-06 | Verfahren zur herstellung von nukleosidalkyl-, aralkyl- und arylphosphoniten und -phosphonaten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3332068A1 true DE3332068A1 (de) | 1985-03-21 |
Family
ID=6208339
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19833332068 Withdrawn DE3332068A1 (de) | 1983-09-06 | 1983-09-06 | Verfahren zur herstellung von nukleosidalkyl-, aralkyl- und arylphosphoniten und -phosphonaten |
| DE8484110314T Expired DE3475307D1 (en) | 1983-09-06 | 1984-08-30 | Method for the preparation of nucleosidealkyl, aralkyl and aryl phosphonites and phosphonates |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE8484110314T Expired DE3475307D1 (en) | 1983-09-06 | 1984-08-30 | Method for the preparation of nucleosidealkyl, aralkyl and aryl phosphonites and phosphonates |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0136543B1 (enExample) |
| JP (2) | JPS6072899A (enExample) |
| AT (1) | ATE38839T1 (enExample) |
| AU (2) | AU570266B2 (enExample) |
| CA (1) | CA1235079A (enExample) |
| DE (2) | DE3332068A1 (enExample) |
| DK (3) | DK162895C (enExample) |
| ES (1) | ES8505384A1 (enExample) |
| GR (1) | GR80287B (enExample) |
| IE (1) | IE57904B1 (enExample) |
| PT (1) | PT79172B (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997042208A1 (en) * | 1996-05-03 | 1997-11-13 | Hybridon, Inc. | In situ preparation of nucleoside phosphoramidites and their use in synthesis of oligonucleotides |
| WO2009021978A3 (de) * | 2007-08-13 | 2009-04-09 | Univ Leipzig | Carbaboranreste enthaltende verbindungen und deren verwendung in der medizin, insbesondere für die verwendung in der tumortherapie |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4959463A (en) * | 1985-10-15 | 1990-09-25 | Genentech, Inc. | Intermediates |
| DE3916871A1 (de) * | 1989-05-24 | 1990-11-29 | Boehringer Mannheim Gmbh | Modifiziertes phosphoramidit-verfahren zur herstellung von modifizierten nukleinsaeuren |
| DK0464638T3 (da) * | 1990-07-02 | 1997-10-13 | Hoechst Ag | Oligonukleotidanaloge med terminale 3-3- eller 5-5-internukleotidbindinger. |
| US5512668A (en) * | 1991-03-06 | 1996-04-30 | Polish Academy Of Sciences | Solid phase oligonucleotide synthesis using phospholane intermediates |
| WO1994002499A1 (en) * | 1992-07-27 | 1994-02-03 | Hybridon, Inc. | Oligonucleotide alkylphosphonothioates |
| US6087491A (en) * | 1993-01-08 | 2000-07-11 | Hybridon, Inc. | Extremely high purity oligonucleotides and methods of synthesizing them using dimer blocks |
| DE69402177T2 (de) * | 1993-01-08 | 1997-06-26 | Hybridon Inc | Synthese von dimer-blöcken und ihre verwendung bei der zusammensetzung von oligonukleotiden |
| NZ262254A (en) * | 1993-01-25 | 1997-10-24 | Hybridon Inc | Oligonucleotide analogue containing a ribonucleotide alkylphosphon(ate or thioate), gene repression |
| CN1088656C (zh) * | 1994-07-26 | 2002-08-07 | 索尼公司 | 图像转印方法 |
| AU707369B2 (en) * | 1995-05-26 | 1999-07-08 | Genta Incorporated | Compositions and methods for the synthesis of organophosphorus derivatives |
| DE102004049339A1 (de) * | 2004-10-08 | 2006-04-13 | Basf Ag | Verfahren zur Reinigung von phosphorhaltigen Chelat-Liganden |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL62834A0 (en) * | 1980-05-14 | 1981-07-31 | Ens Bio Logicals Inc | Polynucleotide synthesis |
| US4415732A (en) * | 1981-03-27 | 1983-11-15 | University Patents, Inc. | Phosphoramidite compounds and processes |
| EP0090789A1 (en) * | 1982-03-26 | 1983-10-05 | Monsanto Company | Chemical DNA synthesis |
| DE3239888A1 (de) * | 1982-10-28 | 1984-05-03 | Hubert Prof. Dr. 2000 Hamburg Köster | Verfahren zur herstellung von oligonucleosidphosphonaten |
-
1983
- 1983-09-06 DE DE19833332068 patent/DE3332068A1/de not_active Withdrawn
-
1984
- 1984-08-30 DE DE8484110314T patent/DE3475307D1/de not_active Expired
- 1984-08-30 AT AT84110314T patent/ATE38839T1/de not_active IP Right Cessation
- 1984-08-30 EP EP84110314A patent/EP0136543B1/de not_active Expired
- 1984-09-04 PT PT79172A patent/PT79172B/pt active IP Right Revival
- 1984-09-04 GR GR80287A patent/GR80287B/el unknown
- 1984-09-04 ES ES535627A patent/ES8505384A1/es not_active Expired
- 1984-09-05 CA CA000462469A patent/CA1235079A/en not_active Expired
- 1984-09-05 JP JP59184717A patent/JPS6072899A/ja active Granted
- 1984-09-05 IE IE2268/84A patent/IE57904B1/en not_active IP Right Cessation
- 1984-09-05 AU AU32756/84A patent/AU570266B2/en not_active Expired
- 1984-09-05 DK DK424784A patent/DK162895C/da active
-
1988
- 1988-02-08 AU AU11384/88A patent/AU601257B2/en not_active Expired
-
1991
- 1991-07-05 DK DK131691A patent/DK167359B1/da active IP Right Grant
- 1991-07-05 DK DK131591A patent/DK166585C/da active
-
1992
- 1992-11-18 JP JP4307481A patent/JPH0662662B2/ja not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997042208A1 (en) * | 1996-05-03 | 1997-11-13 | Hybridon, Inc. | In situ preparation of nucleoside phosphoramidites and their use in synthesis of oligonucleotides |
| WO2009021978A3 (de) * | 2007-08-13 | 2009-04-09 | Univ Leipzig | Carbaboranreste enthaltende verbindungen und deren verwendung in der medizin, insbesondere für die verwendung in der tumortherapie |
Also Published As
| Publication number | Publication date |
|---|---|
| AU570266B2 (en) | 1988-03-10 |
| AU601257B2 (en) | 1990-09-06 |
| DK166585C (da) | 1993-10-25 |
| CA1235079A (en) | 1988-04-12 |
| AU3275684A (en) | 1985-03-14 |
| PT79172A (de) | 1984-10-01 |
| DK162895C (da) | 1992-05-11 |
| DK167359B1 (da) | 1993-10-18 |
| DK162895B (da) | 1991-12-23 |
| DK424784A (da) | 1985-03-07 |
| EP0136543B1 (de) | 1988-11-23 |
| JPH0662662B2 (ja) | 1994-08-17 |
| DK131691A (da) | 1991-07-05 |
| PT79172B (de) | 1986-09-10 |
| EP0136543A2 (de) | 1985-04-10 |
| JPH05262787A (ja) | 1993-10-12 |
| IE842268L (en) | 1985-03-06 |
| DE3475307D1 (en) | 1988-12-29 |
| DK131591A (da) | 1991-07-05 |
| DK424784D0 (da) | 1984-09-05 |
| DK131691D0 (da) | 1991-07-05 |
| JPS6072899A (ja) | 1985-04-24 |
| DK131591D0 (da) | 1991-07-05 |
| DK166585B (da) | 1993-06-14 |
| JPH0531560B2 (enExample) | 1993-05-12 |
| ATE38839T1 (de) | 1988-12-15 |
| ES535627A0 (es) | 1985-05-16 |
| EP0136543A3 (en) | 1986-07-16 |
| GR80287B (en) | 1985-01-07 |
| AU1138488A (en) | 1988-07-14 |
| IE57904B1 (en) | 1993-05-05 |
| ES8505384A1 (es) | 1985-05-16 |
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| 8139 | Disposal/non-payment of the annual fee |