CA2135498A1 - Synthese de monomeres de nucleotide - Google Patents

Synthese de monomeres de nucleotide

Info

Publication number: CA2135498A1
Authority: CA; Canada
Prior art keywords: synthesis; deoxyadenosine; contacting; benzoyl; yield
Prior art date: 1992-05-13
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.): Abandoned

Application number

CA 2135498

Other languages

English (en)

Inventor

Leonid Beigelman

Jasenka Matulic-Adamic

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sirna Therapeutics Inc

Original Assignee

Individual

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.)

1992-05-13

Filing date

1993-05-06

Publication date

1993-11-25

1992-05-13 Priority claimed from US07/882,479 external-priority patent/US5506349A/en

1993-05-06 Application filed by Individual filed Critical Individual

1993-11-25 Publication of CA2135498A1 publication Critical patent/CA2135498A1/fr

Status Abandoned legal-status Critical Current

Links

238000003786 synthesis reaction Methods 0.000 title claims abstract description 50
230000015572 biosynthetic process Effects 0.000 title claims abstract description 43
239000002773 nucleotide Substances 0.000 title description 3
125000003729 nucleotide group Chemical group 0.000 title description 3
239000000178 monomer Substances 0.000 title description 2
238000000034 method Methods 0.000 claims abstract description 64
OCLZPNCLRLDXJC-NTSWFWBYSA-N 2-amino-9-[(2r,5s)-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1CC[C@@H](CO)O1 OCLZPNCLRLDXJC-NTSWFWBYSA-N 0.000 claims abstract description 16
WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 claims abstract description 16
WVXRAFOPTSTNLL-NKWVEPMBSA-N 2',3'-dideoxyadenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1CC[C@@H](CO)O1 WVXRAFOPTSTNLL-NKWVEPMBSA-N 0.000 claims abstract description 8
BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 claims abstract description 7
239000005549 deoxyribonucleoside Substances 0.000 claims abstract 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 72
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 claims description 26
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 17
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 12
239000000203 mixture Substances 0.000 claims description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
-1 alkylsulfonyl chloride Chemical compound 0.000 claims description 8
150000001875 compounds Chemical class 0.000 claims description 8
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 7
GJQBHOAJJGIPRH-UHFFFAOYSA-N benzoyl cyanide Chemical compound N#CC(=O)C1=CC=CC=C1 GJQBHOAJJGIPRH-UHFFFAOYSA-N 0.000 claims description 7
229920005989 resin Polymers 0.000 claims description 7
239000011347 resin Substances 0.000 claims description 7
MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 claims description 7
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 6
238000005915 ammonolysis reaction Methods 0.000 claims description 6
KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 claims description 6
239000003456 ion exchange resin Substances 0.000 claims description 6
229920003303 ion-exchange polymer Polymers 0.000 claims description 6
238000000746 purification Methods 0.000 claims description 6
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
OXTYJSXVUGJSGM-HTVVRFAVSA-N N-Isobutyrylguanosine Chemical compound C1=2NC(NC(=O)C(C)C)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OXTYJSXVUGJSGM-HTVVRFAVSA-N 0.000 claims description 5
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims description 5
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 claims description 5
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 4
125000001453 quaternary ammonium group Chemical group 0.000 claims description 4
238000006894 reductive elimination reaction Methods 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
OOKAXSHFTDPZHP-UHFFFAOYSA-N (1-bromo-2-methyl-1-oxopropan-2-yl) acetate Chemical compound CC(=O)OC(C)(C)C(Br)=O OOKAXSHFTDPZHP-UHFFFAOYSA-N 0.000 claims description 3
VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 claims description 3
229910021529 ammonia Inorganic materials 0.000 claims description 3
230000020176 deacylation Effects 0.000 claims description 3
238000005947 deacylation reaction Methods 0.000 claims description 3
VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 claims description 3
239000002245 particle Substances 0.000 claims description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
QOXJRLADYHZRGC-SHYZEUOFSA-N 1-[(2r,3r,5s)-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O1[C@H](CO)C[C@@H](O)[C@@H]1N1C(=O)NC(=O)C=C1 QOXJRLADYHZRGC-SHYZEUOFSA-N 0.000 claims description 2
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
239000003153 chemical reaction reagent Substances 0.000 claims description 2
230000008569 process Effects 0.000 claims description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 2
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 claims 2
229910052700 potassium Inorganic materials 0.000 claims 2
239000011591 potassium Substances 0.000 claims 2
NAVHPRIPCORUEG-UHFFFAOYSA-N (2-tert-butylphenyl)-chloro-diphenylsilane Chemical compound CC(C)(C)C1=CC=CC=C1[Si](Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 NAVHPRIPCORUEG-UHFFFAOYSA-N 0.000 claims 1
IKMXRUOZUUKSON-UHFFFAOYSA-N 2-(4-nitrophenyl)ethanol Chemical compound OCCC1=CC=C([N+]([O-])=O)C=C1 IKMXRUOZUUKSON-UHFFFAOYSA-N 0.000 claims 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
229910052802 copper Inorganic materials 0.000 claims 1
239000010949 copper Substances 0.000 claims 1
239000011701 zinc Substances 0.000 claims 1
229910052725 zinc Inorganic materials 0.000 claims 1
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 11
DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
239000002777 nucleoside Substances 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
239000007787 solid Substances 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 7
239000000543 intermediate Substances 0.000 description 7
DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 5
125000003835 nucleoside group Chemical group 0.000 description 5
FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 5
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 5
229940045145 uridine Drugs 0.000 description 5
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
238000003818 flash chromatography Methods 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
MRGSDEKKMVPDQM-DTWKUNHWSA-N n-[9-[(2r,5s)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-6-oxo-3h-purin-2-yl]-2-methylpropanamide Chemical compound C1=NC=2C(=O)NC(NC(=O)C(C)C)=NC=2N1[C@@H]1O[C@H](CO)C=C1 MRGSDEKKMVPDQM-DTWKUNHWSA-N 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 3
CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000036436 anti-hiv Effects 0.000 description 3
MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 3
229940093499 ethyl acetate Drugs 0.000 description 3
235000019439 ethyl acetate Nutrition 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
239000000463 material Substances 0.000 description 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
SIDXEQFMTMICKG-DJLDLDEBSA-N n-[9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-oxo-3h-purin-2-yl]-2-methylpropanamide Chemical compound C1=2NC(NC(=O)C(C)C)=NC(=O)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SIDXEQFMTMICKG-DJLDLDEBSA-N 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
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CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
ALGXLPTVRQAONR-YNEHKIRRSA-N [(2r,3s,5r)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] benzoate Chemical compound O([C@H]1C[C@@H](O[C@@H]1CO)N1C=2N=CN=C(C=2N=C1)N)C(=O)C1=CC=CC=C1 ALGXLPTVRQAONR-YNEHKIRRSA-N 0.000 description 2
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FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 2
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
229920001429 chelating resin Polymers 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000012043 crude product Substances 0.000 description 2
229960002656 didanosine Drugs 0.000 description 2
230000000694 effects Effects 0.000 description 2
230000008030 elimination Effects 0.000 description 2
238000003379 elimination reaction Methods 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
230000007717 exclusion Effects 0.000 description 2
239000000284 extract Substances 0.000 description 2
238000002955 isolation Methods 0.000 description 2
150000003833 nucleoside derivatives Chemical class 0.000 description 2
238000005580 one pot reaction Methods 0.000 description 2
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
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125000006239 protecting group Chemical group 0.000 description 2
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229910002027 silica gel Inorganic materials 0.000 description 2
239000002904 solvent Substances 0.000 description 2
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
229960000523 zalcitabine Drugs 0.000 description 2
DPEYHNFHDIXMNV-UHFFFAOYSA-N (9-amino-3-bicyclo[3.3.1]nonanyl)-(4-benzyl-5-methyl-1,4-diazepan-1-yl)methanone dihydrochloride Chemical compound Cl.Cl.CC1CCN(CCN1Cc1ccccc1)C(=O)C1CC2CCCC(C1)C2N DPEYHNFHDIXMNV-UHFFFAOYSA-N 0.000 description 1
CRJFHXYELTYDSG-UHFFFAOYSA-N 1-(4-nitrophenyl)ethanol Chemical compound CC(O)C1=CC=C([N+]([O-])=O)C=C1 CRJFHXYELTYDSG-UHFFFAOYSA-N 0.000 description 1
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OIIFEFOYBUFEFC-HGJMQJFTSA-N 2-amino-9-[(2r,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-3h-purin-6-one Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)C(O)=C1O OIIFEFOYBUFEFC-HGJMQJFTSA-N 0.000 description 1
WREGKURFCTUGRC-UHFFFAOYSA-N 4-Amino-1-[5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1C1OC(CO)CC1 WREGKURFCTUGRC-UHFFFAOYSA-N 0.000 description 1
OOBICGOWICFMIX-POYBYMJQSA-N 4-amino-1-[(2r,5s)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1C=C[C@@H](CO)O1 OOBICGOWICFMIX-POYBYMJQSA-N 0.000 description 1
229930024421 Adenine Natural products 0.000 description 1
239000004342 Benzoyl peroxide Substances 0.000 description 1
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
239000002126 C01EB10 - Adenosine Substances 0.000 description 1
MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
238000001712 DNA sequencing Methods 0.000 description 1
229930010555 Inosine Natural products 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
235000011483 Ribes Nutrition 0.000 description 1
241000220483 Ribes Species 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
241000287433 Turdus Species 0.000 description 1
UPJRDMMVBONKRA-ZZMKVXQQSA-N [(2R,3S,5S)-2-[[tert-butyl(diphenyl)silyl]oxymethyl]-5-(4-methylphenyl)sulfonyl-5-(6-oxo-1H-purin-9-yl)oxolan-3-yl] methanesulfonate Chemical compound [Si](C1=CC=CC=C1)(C1=CC=CC=C1)(C(C)(C)C)OC[C@@H]1[C@H](C[C@@](O1)(N1C=NC=2C(O)=NC=NC1=2)S(=O)(=O)C1=CC=C(C)C=C1)OS(=O)(=O)C UPJRDMMVBONKRA-ZZMKVXQQSA-N 0.000 description 1
GIERFVXRTOJITJ-HJQYOEGKSA-N [(2r,3r,4r,5r)-3-acetyloxy-4-bromo-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl acetate Chemical compound Br[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C(=O)NC(=O)C=C1 GIERFVXRTOJITJ-HJQYOEGKSA-N 0.000 description 1
ORNWXPWLGGXUNT-DJLDLDEBSA-N [(2r,3s,5r)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] acetate Chemical compound O1[C@H](CO)[C@@H](OC(=O)C)C[C@@H]1N1C2=NC=NC(N)=C2N=C1 ORNWXPWLGGXUNT-DJLDLDEBSA-N 0.000 description 1
230000009471 action Effects 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
229960000643 adenine Drugs 0.000 description 1
229960005305 adenosine Drugs 0.000 description 1
150000003838 adenosines Chemical class 0.000 description 1
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
235000019400 benzoyl peroxide Nutrition 0.000 description 1
238000006480 benzoylation reaction Methods 0.000 description 1
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000011097 chromatography purification Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
239000013058 crude material Substances 0.000 description 1
UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
230000006196 deacetylation Effects 0.000 description 1
238000003381 deacetylation reaction Methods 0.000 description 1
RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
229940029575 guanosine Drugs 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
229960003786 inosine Drugs 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
KINOUVLNNBJAKP-CAAJLBCPSA-N n-[9-[(2r,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-6-oxo-3h-purin-2-yl]-2-methylpropanamide Chemical compound C1=2NC(NC(=O)C(C)C)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)C(O)=C1O KINOUVLNNBJAKP-CAAJLBCPSA-N 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
238000006213 oxygenation reaction Methods 0.000 description 1
239000000843 powder Substances 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
239000002212 purine nucleoside Substances 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
210000000614 rib Anatomy 0.000 description 1
239000002342 ribonucleoside Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
238000006884 silylation reaction Methods 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
241000894007 species Species 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
125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000001226 triphosphate Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- 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
- 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
- C07H19/16—Purine radicals

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Saccharide Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA 2135498 1992-05-13 1993-05-06 Synthese de monomeres de nucleotide Abandoned CA2135498A1 (fr)

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
US88257292A	1992-05-13	1992-05-13
US07/882,572		1992-05-13
US07/882,479 US5506349A (en)	1992-05-13	1992-05-13	Chemical synthesis of 2', 3'-dideoxycytidine
US07/882,479		1992-05-13
US91064992A	1992-07-08	1992-07-08
US07/910,649		1992-07-08
US91954492A	1992-07-24	1992-07-24
US07/919,544		1992-07-24

Publications (1)

Publication Number	Publication Date
CA2135498A1 true CA2135498A1 (fr)	1993-11-25

Family

ID=27505972

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA 2135498 Abandoned CA2135498A1 (fr)	1992-05-13	1993-05-06	Synthese de monomeres de nucleotide

Country Status (6)

Country	Link
EP (1)	EP0640091A4 (fr)
JP (1)	JPH07508022A (fr)
AU (1)	AU4234193A (fr)
CA (1)	CA2135498A1 (fr)
MX (1)	MX9302761A (fr)
WO (1)	WO1993023413A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5627160A (en) *	1993-05-25	1997-05-06	Yale University	L-2',3'-dideoxy nucleoside analogs as anti-hepatitis B (HBV) and anti-HIV agents
TW374087B (en) *	1993-05-25	1999-11-11	Univ Yale	L-2',3'-dideoxy nucleotide analogs as anti-hepatitis B(HBV) and anti-HIV agents
WO2007004230A2 (fr) *	2005-07-05	2007-01-11	Hetero Drugs Limited	Nouveau procede de preparation de didanosine au moyen de nouveaux produits intermediaires
CN105884846B (zh) *	2016-06-01	2018-08-28	中南大学	一种2’-脱氧腺苷的合成方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US64631A (en) *		1867-05-14		Thomas g
US5099010A (en) *	1983-01-17	1992-03-24	Research Corporation	Intermediates in the preparation of 3'-amino-2',3'-dideoxycytidine and the pharmacologically acceptable salts thereof
US5084445A (en) *	1986-05-01	1992-01-28	University Of Georgia Research Foundation, Inc.	3'-azido-2',3'-dideoxy-5-methylcytidine
JPS63275597A (ja) *	1987-05-07	1988-11-14	Ajinomoto Co Inc	ジデオキシシチジンの製造方法、その製造中間体、およびその製造方法
US4987224A (en) *	1988-08-02	1991-01-22	University Of Georgia Research Foundation, Inc.	Method of preparation of 2',3'-dideoxynucleosides

1993
- 1993-05-06 AU AU42341/93A patent/AU4234193A/en not_active Abandoned
- 1993-05-06 CA CA 2135498 patent/CA2135498A1/fr not_active Abandoned
- 1993-05-06 JP JP6503628A patent/JPH07508022A/ja active Pending
- 1993-05-06 WO PCT/US1993/004239 patent/WO1993023413A1/fr not_active Ceased
- 1993-05-06 EP EP93911072A patent/EP0640091A4/fr not_active Withdrawn
- 1993-05-12 MX MX9302761A patent/MX9302761A/es unknown

Also Published As

Publication number	Publication date
EP0640091A4 (fr)	1995-07-26
MX9302761A (es)	1994-05-31
JPH07508022A (ja)	1995-09-07
WO1993023413A1 (fr)	1993-11-25
EP0640091A1 (fr)	1995-03-01
AU4234193A (en)	1993-12-13

Legal Events

Date	Code	Title	Description
1997-05-06	FZDE	Dead

Publication	Publication Date	Title
AU2001286959B2 (en)	2007-09-06	Methods for synthesizing nucleosides, nucleoside derivatives and non-nucleoside derivatives
RU2211223C2 (ru)	2003-08-27	Новые нуклеозиды, имеющие бициклическую сахарную группировку, и содержащие их олигонуклеотиды
US6130326A (en)	2000-10-10	Monocyclic L-Nucleosides, analogs and uses thereof
Mansuri et al.	1989	Preparation of 1-(2, 3-dideoxy-. beta.-D-glycero-pent-2-enofuranosyl) thymine (d4T) and 2', 3'-dideoxyadenosine (ddA): general methods for the synthesis of 2', 3'-olefinic and 2', 3'-dideoxy nucleoside analogs active against HIV
Morvan et al.	1987	α-DNA II. Synthesis of unnatural α-anomeric oligodeoxyribonucleotides containing the four usual bases and study of their substrate activities for nucleases
US6525191B1 (en)	2003-02-25	Conformationally constrained L-nucleosides
EP1161439B1 (fr)	2010-04-21	Analogues de xylo-lna
AU2001286959A1 (en)	2002-06-06	Methods for synthesizing nucleosides, nucleoside derivatives and non-nucleoside derivatives
US20020150936A1 (en)	2002-10-17	Methods for synthesizing nucleosides, nucleoside derivatives and non-nucleoside derivatives
Robins et al.	1995	Nucleic Acid-Related Compounds. 88. Efficient Conversions of Ribonucleosides into Their 2', 3'-Anhydro, 2'(and 3')-Deoxy, 2', 3'-Didehydro-2', 3'-dideoxy, and 2', 3'-Dideoxynucleoside Analogs
Sugimura et al.	1994	Stereoselective Synthesis of 2'-Deoxy-. beta.-D-threo-pentofuranosyl Nucleosides by the NBS-Promoted Coupling Reaction of Thioglycosides with Silylated Heterocyclic Bases
Allart et al.	1999	Synthesis of protected D-altritol nucleosides as building blocks for oligonucleotide synthesis
EP0720604B1 (fr)	1997-11-19	Analogues de nucleosides de conformation verrouillee
JPH04501558A (ja)	1992-03-19	２’、３’―ジデオキシヌクレオシドの調製方法
US5864031A (en)	1999-01-26	Process for preparing 5-dithio-modified oligonucleotides
KR20030092037A (ko)	2003-12-03	2'-할로-β-Ｌ-아라비노퓨라노실 뉴클레오사이드의 제조방법
AU4234193A (en)	1993-12-13	Synthesis of nucleotide monomers
US5290927A (en)	1994-03-01	Process for preparing 2',3'-dideoxyadenosine
US5175267A (en)	1992-12-29	Stereoselective glycosylation of hetercyclic bases
EP0799834A1 (fr)	1997-10-08	Nucléosides modifiés
EP0686150B1 (fr)	1998-05-20	Procédé pour la préparation des C-nucléosides et des analogues, nouveaux C-nucléosides et des analogues et leur utilisation
AppDNA	2016	3.4. 5 Modified Oligonucleotides
JPH07157496A (ja)	1995-06-20	デオキシヌクレオシドの製造法
Wang	1992	Synthesis of oligonucleotides containing a sulfide or sulfone backbone for binding & nuclease stability studies
WO1995001986A1 (fr)	1995-01-19	Didesoxyfructonucleotides et desoxyfructonucleotides servant de substrats de l'adn-polymerase