CA2291688C - Novel sulfur transfer reagents for oligonucleotide synthesis - Google Patents
Novel sulfur transfer reagents for oligonucleotide synthesis Download PDFInfo
- Publication number
- CA2291688C CA2291688C CA002291688A CA2291688A CA2291688C CA 2291688 C CA2291688 C CA 2291688C CA 002291688 A CA002291688 A CA 002291688A CA 2291688 A CA2291688 A CA 2291688A CA 2291688 C CA2291688 C CA 2291688C
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- dithiazole
- thione
- amino
- organic 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.)
- Expired - Lifetime
Links
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 64
- 238000012546 transfer Methods 0.000 title claims abstract description 61
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 229910052717 sulfur Inorganic materials 0.000 title claims abstract description 48
- 239000011593 sulfur Substances 0.000 title claims abstract description 46
- 238000002515 oligonucleotide synthesis Methods 0.000 title description 5
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract description 48
- 150000001875 compounds Chemical class 0.000 claims abstract description 27
- YWZHEXZIISFIDA-UHFFFAOYSA-N 5-amino-1,2,4-dithiazole-3-thione Chemical compound NC1=NC(=S)SS1 YWZHEXZIISFIDA-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 125000000962 organic group Chemical group 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 45
- 238000003786 synthesis reaction Methods 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 36
- 230000015572 biosynthetic process Effects 0.000 claims description 34
- 230000008569 process Effects 0.000 claims description 31
- 238000005987 sulfurization reaction Methods 0.000 claims description 26
- 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 description 23
- 239000005864 Sulphur Substances 0.000 claims description 9
- 125000004354 sulfur functional group Chemical group 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 4
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 abstract description 11
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 abstract description 11
- JUDOLRSMWHVKGX-UHFFFAOYSA-N 1,1-dioxo-1$l^{6},2-benzodithiol-3-one Chemical compound C1=CC=C2C(=O)SS(=O)(=O)C2=C1 JUDOLRSMWHVKGX-UHFFFAOYSA-N 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 3
- 238000011160 research Methods 0.000 abstract description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 abstract description 2
- 238000005457 optimization Methods 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 238000013459 approach Methods 0.000 description 15
- 150000008300 phosphoramidites Chemical class 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 229940125904 compound 1 Drugs 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 239000002777 nucleoside Substances 0.000 description 6
- -1 pyridine-CH3CN (1:9) Chemical compound 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- 230000000692 anti-sense effect Effects 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 125000003835 nucleoside group Chemical group 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 150000004713 phosphodiesters Chemical class 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 150000005829 chemical entities Chemical class 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- PWWSSIYVTQUJQQ-UHFFFAOYSA-N distearyl thiodipropionate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCSCCC(=O)OCCCCCCCCCCCCCCCCCC PWWSSIYVTQUJQQ-UHFFFAOYSA-N 0.000 description 2
- AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 150000008298 phosphoramidates Chemical class 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- BPVALDZRWMHTCJ-UHFFFAOYSA-N 1,2,4-dithiazolidine-3,5-dione Chemical compound O=C1NC(=O)SS1 BPVALDZRWMHTCJ-UHFFFAOYSA-N 0.000 description 1
- AEHGOWVFQLOENS-UHFFFAOYSA-N 1-methyl-4-[(4-methylphenyl)sulfonyldisulfanyl]sulfonylbenzene Chemical compound C1=CC(C)=CC=C1S(=O)(=O)SSS(=O)(=O)C1=CC=C(C)C=C1 AEHGOWVFQLOENS-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- TXLINXBIWJYFNR-UHFFFAOYSA-N 4-phenylpyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC(C=2C=CC=CC=2)=C1 TXLINXBIWJYFNR-UHFFFAOYSA-N 0.000 description 1
- RZIJZXUDFRSADE-UHFFFAOYSA-N 5-ethoxy-1,2,4-dithiazol-3-one Chemical compound CCOC1=NC(=O)SS1 RZIJZXUDFRSADE-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000028257 Joubert syndrome with oculorenal defect Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- VBQDSLGFSUGBBE-UHFFFAOYSA-N benzyl(triethyl)azanium Chemical compound CC[N+](CC)(CC)CC1=CC=CC=C1 VBQDSLGFSUGBBE-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 150000002500 ions Chemical group 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 150000002972 pentoses Chemical group 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- SXADIBFZNXBEGI-UHFFFAOYSA-N phosphoramidous acid Chemical compound NP(O)O SXADIBFZNXBEGI-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical class 0.000 description 1
- IXGZXXBJSZISOO-UHFFFAOYSA-N s-(2-phenylacetyl)sulfanyl 2-phenylethanethioate Chemical compound C=1C=CC=CC=1CC(=O)SSC(=O)CC1=CC=CC=C1 IXGZXXBJSZISOO-UHFFFAOYSA-N 0.000 description 1
- XTDHBAVVPOKCKF-UHFFFAOYSA-N s-(benzoyltrisulfanyl) benzenecarbothioate Chemical compound C=1C=CC=CC=1C(=O)SSSSC(=O)C1=CC=CC=C1 XTDHBAVVPOKCKF-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/15—Six-membered rings
- C07D285/16—Thiadiazines; Hydrogenated thiadiazines
-
- 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)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/865,666 | 1997-05-30 | ||
| US08/865,666 US6096881A (en) | 1997-05-30 | 1997-05-30 | Sulfur transfer reagents for oligonucleotide synthesis |
| PCT/US1998/010653 WO1998054198A1 (en) | 1997-05-30 | 1998-05-26 | Novel sulfur transfer reagents for oligonucleotide synthesis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2291688A1 CA2291688A1 (en) | 1998-12-03 |
| CA2291688C true CA2291688C (en) | 2008-01-29 |
Family
ID=25345990
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002291688A Expired - Lifetime CA2291688C (en) | 1997-05-30 | 1998-05-26 | Novel sulfur transfer reagents for oligonucleotide synthesis |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6096881A (https=) |
| EP (1) | EP0986571B1 (https=) |
| JP (1) | JP4393594B2 (https=) |
| AT (1) | ATE271065T1 (https=) |
| AU (1) | AU7597498A (https=) |
| CA (1) | CA2291688C (https=) |
| DE (1) | DE69825051T2 (https=) |
| ES (1) | ES2226135T3 (https=) |
| WO (1) | WO1998054198A1 (https=) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0992506B1 (en) * | 1998-10-08 | 2003-08-06 | Novartis AG | Process for the sulfurisation of phosphorus-containing compounds |
| US7098325B2 (en) * | 1998-10-08 | 2006-08-29 | Pierre Martin | Process for the sulfurization of a phosphorus-containing compound |
| GB0004889D0 (en) | 2000-03-01 | 2000-04-19 | Avecia Ltd | Synthesis of oligonucleotides |
| US6768005B2 (en) * | 2000-12-20 | 2004-07-27 | Avecia Limited | Process |
| WO2002046205A2 (en) * | 2000-12-05 | 2002-06-13 | Avecia Limited | Process for the preparation of phosphorothionate oligonucleotides |
| AR036122A1 (es) * | 2001-07-03 | 2004-08-11 | Avecia Biotechnology Inc | Un complejo de sal que comprende un n-alquilimidazol y una 1,1-dioxo-1,2-dihidro-1l6-benzo [d]-isotiazol-3-ona y un metodo para sintetizar oligonucleotidos utilizando la quimica de fosforamidita |
| JP4825375B2 (ja) * | 2001-08-28 | 2011-11-30 | 株式会社 資生堂 | ジチアゾール化合物及びマトリックスメタロプロテアーゼ活性阻害剤、皮膚外用剤 |
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| WO2005097817A2 (en) * | 2004-04-05 | 2005-10-20 | Alnylam Pharmaceuticals, Inc. | Process and reagents for oligonucleotide synthesis and purification |
| CN104086516B (zh) * | 2014-07-18 | 2016-01-06 | 成都樵枫科技发展有限公司 | R-(+)-硫代四氢呋喃-2-甲酸的合成方法 |
| CN110199023A (zh) | 2016-12-28 | 2019-09-03 | 第一三共株式会社 | 阿尔波特氏综合症治疗药 |
| WO2019111791A1 (ja) * | 2017-12-07 | 2019-06-13 | 第一三共株式会社 | ジストロフィン遺伝子のイントロンリテンションを解消するアンチセンスオリゴヌクレオチド |
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| BR112021024764A2 (pt) | 2019-07-12 | 2022-04-19 | Daiichi Sankyo Co Ltd | Oligonucleotídeo antissenso capaz de alterar o splicing de pré-mrna de dux4 |
| WO2021049504A1 (ja) | 2019-09-10 | 2021-03-18 | 第一三共株式会社 | 肝臓送達用ＧａｌＮＡｃ－オリゴヌクレオチドコンジュゲートおよび製造方法 |
| IL292286A (en) | 2019-10-18 | 2022-06-01 | Daiichi Sankyo Co Ltd | Production method for bicyclic phosphoramidite |
| EP4119167A4 (en) | 2020-03-11 | 2025-08-06 | Biocomber Co Ltd | SINGLE-STRANDED NUCLEIC ACID MOLECULE FOR INDUCING FRAME SHIFT-1 AND COMPOSITION |
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| EP4261284A4 (en) | 2020-12-08 | 2025-07-16 | Univ Fukuoka | STABLE TARGET EDITING GUIDE RNA INTO WHICH A CHEMICALLY MODIFIED NUCLEIC ACID HAS BEEN INTRODUCED |
| US20240229036A9 (en) | 2021-02-26 | 2024-07-11 | Knc Laboratories Co., Ltd. | Nucleic acid medicine expressing splicing variant of myostatin |
| JPWO2023176863A1 (https=) | 2022-03-16 | 2023-09-21 | ||
| KR20240161967A (ko) | 2022-03-16 | 2024-11-13 | 다이이찌 산쿄 가부시키가이샤 | 트랜스페린 수용체 2 의 발현을 억제하는 siRNA |
| TW202523839A (zh) | 2023-08-25 | 2025-06-16 | 學校法人福岡大學 | 導入有磷酸部修飾之穩定型標靶編輯引導ｒｎａ |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3753908A (en) * | 1971-08-30 | 1973-08-21 | Chevron Res | Oxidation inhibited lubricating oil compositions with extreme pressure properties |
| DE4320157A1 (de) * | 1993-06-18 | 1994-12-22 | Bayer Ag | Verwendung von 1,2,4-Dithiazolium-Salzen als Chemotherapeutica |
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1997
- 1997-05-30 US US08/865,666 patent/US6096881A/en not_active Expired - Lifetime
-
1998
- 1998-05-26 CA CA002291688A patent/CA2291688C/en not_active Expired - Lifetime
- 1998-05-26 AU AU75974/98A patent/AU7597498A/en not_active Abandoned
- 1998-05-26 JP JP50080299A patent/JP4393594B2/ja not_active Expired - Lifetime
- 1998-05-26 EP EP98923757A patent/EP0986571B1/en not_active Expired - Lifetime
- 1998-05-26 DE DE69825051T patent/DE69825051T2/de not_active Expired - Lifetime
- 1998-05-26 ES ES98923757T patent/ES2226135T3/es not_active Expired - Lifetime
- 1998-05-26 AT AT98923757T patent/ATE271065T1/de not_active IP Right Cessation
- 1998-05-26 WO PCT/US1998/010653 patent/WO1998054198A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| CA2291688A1 (en) | 1998-12-03 |
| ATE271065T1 (de) | 2004-07-15 |
| JP2002501534A (ja) | 2002-01-15 |
| DE69825051T2 (de) | 2005-10-06 |
| EP0986571A1 (en) | 2000-03-22 |
| DE69825051D1 (de) | 2004-08-19 |
| AU7597498A (en) | 1998-12-30 |
| ES2226135T3 (es) | 2005-03-16 |
| WO1998054198A1 (en) | 1998-12-03 |
| US6096881A (en) | 2000-08-01 |
| JP4393594B2 (ja) | 2010-01-06 |
| WO1998054198A9 (en) | 1999-04-01 |
| EP0986571B1 (en) | 2004-07-14 |
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