JPH09508135A - 不斉リン酸ジエステル及びその塩の製造方法 - Google Patents
不斉リン酸ジエステル及びその塩の製造方法Info
- Publication number
- JPH09508135A JPH09508135A JP7519873A JP51987395A JPH09508135A JP H09508135 A JPH09508135 A JP H09508135A JP 7519873 A JP7519873 A JP 7519873A JP 51987395 A JP51987395 A JP 51987395A JP H09508135 A JPH09508135 A JP H09508135A
- Authority
- JP
- Japan
- Prior art keywords
- halogen
- alkyl
- hydrogen
- residue
- salt
- 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.)
- Granted
Links
- -1 phosphoric acid diester Chemical class 0.000 title claims abstract description 69
- 238000000034 method Methods 0.000 title claims abstract description 39
- 150000003839 salts Chemical class 0.000 title claims abstract description 37
- 229910000147 aluminium phosphate Inorganic materials 0.000 title claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 title claims description 8
- 239000002253 acid Substances 0.000 claims abstract description 28
- 239000012043 crude product Substances 0.000 claims abstract description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 17
- 239000003960 organic solvent Substances 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- 150000002500 ions Chemical class 0.000 claims abstract description 7
- 229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 6
- 239000011707 mineral Substances 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 150000002367 halogens Chemical class 0.000 claims description 42
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000001369 canonical nucleoside group Chemical group 0.000 claims description 8
- 239000002244 precipitate Substances 0.000 claims description 7
- UXCAQJAQSWSNPQ-XLPZGREQSA-N Alovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](F)C1 UXCAQJAQSWSNPQ-XLPZGREQSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 150000003014 phosphoric acid esters Chemical class 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 5
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 3
- AVEGLFHOBOAVIJ-UHFFFAOYSA-N 2-amino-9-(ethoxymethyl)-3h-purin-6-one Chemical group N1=C(N)NC(=O)C2=C1N(COCC)C=N2 AVEGLFHOBOAVIJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 150000001540 azides Chemical group 0.000 claims description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 3
- QMWIWOKPCMKRHL-UHFFFAOYSA-N 2,6-di(propan-2-yl)benzenesulfonyl chloride Chemical compound CC(C)C1=CC=CC(C(C)C)=C1S(Cl)(=O)=O QMWIWOKPCMKRHL-UHFFFAOYSA-N 0.000 claims description 2
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 claims description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 2
- 229910001424 calcium ion Inorganic materials 0.000 claims description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical compound CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000003473 lipid group Chemical group 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 23
- 150000002632 lipids Chemical class 0.000 abstract description 14
- 229910019142 PO4 Inorganic materials 0.000 abstract description 13
- 238000001704 evaporation Methods 0.000 abstract description 11
- 230000008020 evaporation Effects 0.000 abstract description 11
- 150000007530 organic bases Chemical class 0.000 abstract description 9
- 239000010452 phosphate Substances 0.000 abstract description 9
- 238000004237 preparative chromatography Methods 0.000 abstract description 4
- 230000007062 hydrolysis Effects 0.000 abstract description 3
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 3
- 150000003222 pyridines Chemical class 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 239000002904 solvent Substances 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000002777 nucleoside Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 20
- 230000008018 melting Effects 0.000 description 19
- 238000002844 melting Methods 0.000 description 19
- 125000003835 nucleoside group Chemical group 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 238000000354 decomposition reaction Methods 0.000 description 16
- 239000012071 phase Substances 0.000 description 13
- 159000000000 sodium salts Chemical class 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 238000009833 condensation Methods 0.000 description 12
- 230000005494 condensation Effects 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 235000021317 phosphate Nutrition 0.000 description 10
- 229960002555 zidovudine Drugs 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 239000011575 calcium Substances 0.000 description 7
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 7
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 6
- 150000004713 phosphodiesters Chemical class 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 159000000007 calcium salts Chemical class 0.000 description 4
- GRJCIXKOALIDNC-UHFFFAOYSA-N (2-decoxy-3-dodecylsulfanylpropyl) dihydrogen phosphate Chemical compound CCCCCCCCCCCCSCC(COP(O)(O)=O)OCCCCCCCCCC GRJCIXKOALIDNC-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 3
- XQKKWWCELHKGKB-UHFFFAOYSA-L calcium acetate monohydrate Chemical compound O.[Ca+2].CC([O-])=O.CC([O-])=O XQKKWWCELHKGKB-UHFFFAOYSA-L 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
- NKGPJODWTZCHGF-KQYNXXCUSA-N 6-thioinosinic acid Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(S)=C2N=C1 NKGPJODWTZCHGF-KQYNXXCUSA-N 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- NJLHHACGWKAWKL-UHFFFAOYSA-N ClP(Cl)=O Chemical compound ClP(Cl)=O NJLHHACGWKAWKL-UHFFFAOYSA-N 0.000 description 2
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000015439 Phospholipases Human genes 0.000 description 2
- 108010064785 Phospholipases Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241000187747 Streptomyces Species 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000005228 aryl sulfonate group Chemical group 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
- 239000001639 calcium acetate Substances 0.000 description 2
- 229960005147 calcium acetate Drugs 0.000 description 2
- 235000011092 calcium acetate Nutrition 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 229960002656 didanosine Drugs 0.000 description 2
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical group CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- RBBIKFDLPCEOTF-UHFFFAOYSA-N 2,3,4-tri(propan-2-yl)benzenesulfonic acid Chemical compound CC(C)C1=CC=C(S(O)(=O)=O)C(C(C)C)=C1C(C)C RBBIKFDLPCEOTF-UHFFFAOYSA-N 0.000 description 1
- HRBGUGQWTMBDTR-UHFFFAOYSA-N 2,3,4-tri(propan-2-yl)benzenesulfonyl chloride Chemical compound CC(C)C1=CC=C(S(Cl)(=O)=O)C(C(C)C)=C1C(C)C HRBGUGQWTMBDTR-UHFFFAOYSA-N 0.000 description 1
- YGHTUAYWROAHCD-UHFFFAOYSA-N 2,3-di(undecoxy)propyl dihydrogen phosphate Chemical compound CCCCCCCCCCCOCC(COP(O)(O)=O)OCCCCCCCCCCC YGHTUAYWROAHCD-UHFFFAOYSA-N 0.000 description 1
- PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 1
- JSJRZORDGWPGCU-UHFFFAOYSA-N 2,6-di(propan-2-yl)benzenesulfonic acid Chemical compound CC(C)C1=CC=CC(C(C)C)=C1S(O)(=O)=O JSJRZORDGWPGCU-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 229910021532 Calcite Inorganic materials 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- VAPZPBBPRKQWNR-AKGZTFGVSA-N OCC(O)CP(=O)=N[C@@H](CO)C(O)=O Chemical compound OCC(O)CP(=O)=N[C@@H](CO)C(O)=O VAPZPBBPRKQWNR-AKGZTFGVSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 1
- OIFWQOKDSPDILA-XLPZGREQSA-N [(2s,3s,5r)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl dihydrogen phosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](N=[N+]=[N-])C1 OIFWQOKDSPDILA-XLPZGREQSA-N 0.000 description 1
- AGVKRJMCCLIOGE-ZRGJLLHDSA-N [Na].C(CC)OP(=O)(OOC(C)C(CCCCCCC)SCCCCCCCCCC)OC[C@@H]1CC[C@@H](O1)N1C(=O)NC(=O)C(C)=C1 Chemical compound [Na].C(CC)OP(=O)(OOC(C)C(CCCCCCC)SCCCCCCCCCC)OC[C@@H]1CC[C@@H](O1)N1C(=O)NC(=O)C(C)=C1 AGVKRJMCCLIOGE-ZRGJLLHDSA-N 0.000 description 1
- VSGHJWUIUWCVJE-DSDMQBBUSA-N [Na].C(CC)OP(=O)(OOC(C)C(CCCCCCC)SCCCCCCCCCCCC)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C(=O)NC(=O)C(=C1)F)O)O Chemical compound [Na].C(CC)OP(=O)(OOC(C)C(CCCCCCC)SCCCCCCCCCCCC)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C(=O)NC(=O)C(=C1)F)O)O VSGHJWUIUWCVJE-DSDMQBBUSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 125000006612 decyloxy group Chemical group 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000000039 preparative column chromatography Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229940113082 thymine Drugs 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
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- 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
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
-
- 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
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Fuel Cell (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.不斉リン酸ジエステルの生成方法であって、 (a)下記式(I): R1−O−P(O)(OH)2 (I) 〔式中、R1は有機残基を表わす〕で表わされるリン酸エステルが、下記式(II ): R2−OH (II) 〔式中、R2は有機残基を表わす〕により、アリールスルホン酸クロリド及び有 機相の存在下で縮合され、 (b)形成されるリン酸ジエステルが、アルカリ土類イオンを含む溶液の添加 により控えめの溶解性の塩として沈殿され、そしてそれが単離され、 (c)前記控えめの溶解性の塩が、水−不混和性有機溶媒及び希釈水性鉱酸に おける懸濁液により有機溶媒における遊離酸として単離されることを含んで成る 方法。 2.前記段階(a)−(c)の後、得られる粗生成物を分離用クロマトグラフ ィーにより精製し(段階(d))、そして所望により、遊離酸として得られた化 合物を続いて、いづれかの所望する塩に転換する(段階(e))請求の範囲第1 項記載の方法。 3.前記アルカリ土類イオンを含む溶液が、カルシウムイオンを含む溶液であ る請求の範囲第1又は2項記載の方法。 4.ベンゼン−、トルエン−、2,4,6−トリメチルベンゼン−、2,6− ジメチルベンゼン−、2,4,6−トリイソプロピルベンゼン−又は2,6−ジ イソプロピルベンゼン−スルホン酸クロリドが、前記アリールスルホン酸クロリ ドとして使用される請求の範囲第1〜3のいづれか1項記載の方法。 5.R1が下記一般式(IV): 〔式中、A及びBは同じであっても又は異なっていても良く、そして水素、C1 −C18アルキル、C1−C18アルコキシ、C1−C18アルキルチオ、C1−C18ア ルキルスルフィニル又はC1−C18アルキルスルホニルを表わす〕で表わされる 脂質残基を表わし、又は R1が、所望により、ハロゲン、C1−C6アルコキシ、C1−C6アルキルメル カプトにより1度又は数度置換され得る、10〜20個の炭素原子を有する直鎖又は 枝分れ鎖の、飽和又は不飽和アルキル鎖を表わすリン酸エステルが使用される請 求の範囲第1〜4のいづれか1項記載の方法。 6.R1が一般式(IV)〔式中、A及びBはお互い異なっており、そしてC10 −C16アルコキシ及びC10−C16アルキルチオを表わす〕で表わされる脂質残基 を表わすリン酸エステルが使用される請求の範囲第1〜5のいづれか1項記載の 方法。 7.R2が、下記一般式(V): 〔式中、R3は水素、ハロゲン又はヒドロキシ基を表わし、 R4及びR5は個々に、水素を表わし、又はR4及びR5の1つはハロゲン、ヒド ロキシ、シアノ、アミノ又はアジド基を表わし、そしてR3及びR4はさらに、C −2’とC−3’との間で追加の 結合を表わすことができ、 R5は水素、ヒドロキシ、アシド、アミノ、シアノ又はハロゲンを表わす〕で 表わされる5’ヌクレオシド残基を表わし、 又はそれは、下記一般式(Va): 〔式中、Rは水素原子又はC1−C3アルキル基を表わし、ここでアルキル基は所 望によりヒドロキシ、ハロゲン又はアジドにより置換され、そしてBは次の化合 物の1つを表わし: 1.) 〔式中、R6は水素、1〜4個の炭素原子を有するアルキル鎖(ハロゲン、又は 所望によりハロゲンにより置換され得る、2〜6個の炭素原子を有するアルケニ ル又はアルキニル残基により置換され得る)、又はハロゲンであり得る〕、 2.) 〔式中、R7は水素、1〜4個の炭素原子を有するアルキル鎖(ハロゲンにより 置換され得る)又はハロゲンであり得る〕、 3.) 〔式中、R8は、水素、1〜4個の炭素原子を有するアルキル鎖、ハロゲン、ヒ ドロキシ又はアミノ基であり得る〕、 4.) 〔式中、R9は水素、ハロゲン又はアミノ基であり、そして R10は水素、ハロゲン、メルカプト、C1−C6アルコキシ、C1−C6アルキル メルカプト又はアミノ基を表わし、ここで前記基は、C1−C6アルキル、C1− C6アルコキシ、ヒドロキシ、C2−C6アルキル及び/又はC3−C6シクロアル キル、アリール、ヘタリール、アラルキル又はヘタリールアルキル基により一又 は二置換され得、ここで所望により、前記アリール又はヘタリール残基において 、1又は複数のヒドロキシ、メトキシ又はアルキル基又はハロゲンによりさらに 置換され得、又はR9は所望により、モノアルキルもしくはジアルキル、又はア ルコキシ基により置換され得るアリル基を表わす〕 で表わされる第2−ヌクレオシド残基を表わす化合物IIが使用される請求の範囲 第1〜6〜いづれか1項記載の方法。 8.R2が3’−デオキシ−3’−アジドチミジン、3’−デオキシ−3’− フルオロチミジン、5−フルオロウリジン、6−メル カプトプリン−9−β−D−リボフラノシド、6−メチルメルカプトプリン−9 −β−D−リボフラノシド、9−{〔(1−ヒドロキシメチル)エトキシ〕−メ チル}グアニン又は9−(エトキシメチル)グアニン残基である化合物IIが使用 される請求の範囲第7項記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4402492.4 | 1994-01-28 | ||
DE4402492A DE4402492A1 (de) | 1994-01-28 | 1994-01-28 | Verfahren zur Herstellung von unsymmetrischen Phosphorsäurediestern |
PCT/EP1995/000219 WO1995020596A1 (de) | 1994-01-28 | 1995-01-21 | Verfahren zur herstellung von unsymmetrischen phosphorsäurediestern |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH09508135A true JPH09508135A (ja) | 1997-08-19 |
JP3609411B2 JP3609411B2 (ja) | 2005-01-12 |
Family
ID=6508875
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP51987395A Expired - Fee Related JP3609411B2 (ja) | 1994-01-28 | 1995-01-21 | 不斉リン酸ジエステル及びその塩の製造方法 |
Country Status (17)
Country | Link |
---|---|
US (1) | US5734042A (ja) |
EP (1) | EP0741740B1 (ja) |
JP (1) | JP3609411B2 (ja) |
KR (1) | KR100242357B1 (ja) |
AT (1) | ATE178610T1 (ja) |
AU (1) | AU1417195A (ja) |
BR (1) | BR9506654A (ja) |
CA (1) | CA2181474C (ja) |
DE (2) | DE4402492A1 (ja) |
DK (1) | DK0741740T3 (ja) |
ES (1) | ES2132618T3 (ja) |
FI (1) | FI115836B (ja) |
HU (1) | HU222438B1 (ja) |
PL (1) | PL179560B1 (ja) |
SI (1) | SI9520031A (ja) |
TW (1) | TW399059B (ja) |
WO (1) | WO1995020596A1 (ja) |
Families Citing this family (4)
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ES2239761T3 (es) * | 1994-11-12 | 2005-10-01 | Heidelberg Pharma Gmbh | Complejo de enzima que desdobla lipidos. |
US7026469B2 (en) | 2000-10-19 | 2006-04-11 | Wake Forest University School Of Medicine | Compositions and methods of double-targeting virus infections and cancer cells |
GB0608876D0 (en) | 2006-05-05 | 2006-06-14 | Medivir Ab | Combination therapy |
WO2021198725A1 (de) | 2020-03-30 | 2021-10-07 | Chiracon Gmbh | Fosalvudin und fozivudintidoxil zur anwendung bei der behandlung der krankheit covid-19 und die verwendung von deren strukturvereinfachten derivaten |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5289681A (en) * | 1976-01-22 | 1977-07-27 | Yamasa Shoyu Co Ltd | Preparation of aracytidine -5# phosphoric acid ester derivatives |
JPS552601A (en) * | 1978-06-20 | 1980-01-10 | Yamasa Shoyu Co Ltd | Anti-tumor agent for non-injection use |
WO1991012256A1 (en) * | 1990-02-09 | 1991-08-22 | Istituto Chemioterapico Italiano Fine Chemicals S.P.A. | Process for preparing l-alpha-glycerylphosphoryl-d-myoinositol and its salts |
WO1991015494A1 (en) * | 1990-03-30 | 1991-10-17 | Istituto Chemioterapico Italiano Fine Chemicals S.P.A. | Process for separating the main components of a mixture of raw deacylated phospholipids |
JPH07291982A (ja) * | 1992-06-24 | 1995-11-07 | Chemi Spa | グリセロりん脂質の製造方法 |
JPH08500345A (ja) * | 1992-08-08 | 1996-01-16 | ベーリンガー マンハイム ゲーエムベーハー | セコ‐ヌクレオシドのリポヌクレオチド、その製法及びその抗ウィルス製剤としての使用 |
JPH08512040A (ja) * | 1993-07-01 | 1996-12-17 | ベーリンガー マンハイム ゲゼルシャフト ミット ベシュレンクテル ハフツング | デオキシヌクレオシドのリポヌクレオチド、それらの製造方法および抗ウイルス薬としてのそれらの用途 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS552602A (en) * | 1978-06-20 | 1980-01-10 | Yamasa Shoyu Co Ltd | 1-beta-d-arabinofranosylcytosine-5'-phosphoric acid oleyl ester |
DD138213A1 (de) * | 1978-08-03 | 1979-10-17 | Hans Brachwitz | Verfahren zur herstellung von 1-0-alkyl(acyl)-3-chlor-3-desoxy-glycero-2-phosphorsaeure-omega-halogenalkylestern |
EP0081386B1 (en) * | 1981-12-09 | 1985-05-29 | Teijin Limited | 5-fluoro-2'-deoxyuridine derivatives and a process for the preparation thereof |
-
1994
- 1994-01-28 DE DE4402492A patent/DE4402492A1/de not_active Withdrawn
-
1995
- 1995-01-21 ES ES95905641T patent/ES2132618T3/es not_active Expired - Lifetime
- 1995-01-21 DE DE59505592T patent/DE59505592D1/de not_active Expired - Lifetime
- 1995-01-21 AT AT95905641T patent/ATE178610T1/de not_active IP Right Cessation
- 1995-01-21 US US08/682,571 patent/US5734042A/en not_active Expired - Lifetime
- 1995-01-21 EP EP95905641A patent/EP0741740B1/de not_active Expired - Lifetime
- 1995-01-21 WO PCT/EP1995/000219 patent/WO1995020596A1/de active IP Right Grant
- 1995-01-21 JP JP51987395A patent/JP3609411B2/ja not_active Expired - Fee Related
- 1995-01-21 KR KR1019960704058A patent/KR100242357B1/ko not_active IP Right Cessation
- 1995-01-21 PL PL95315671A patent/PL179560B1/pl not_active IP Right Cessation
- 1995-01-21 BR BR9506654A patent/BR9506654A/pt not_active IP Right Cessation
- 1995-01-21 DK DK95905641T patent/DK0741740T3/da active
- 1995-01-21 AU AU14171/95A patent/AU1417195A/en not_active Abandoned
- 1995-01-21 CA CA002181474A patent/CA2181474C/en not_active Expired - Fee Related
- 1995-01-21 HU HU9602062A patent/HU222438B1/hu not_active IP Right Cessation
- 1995-01-21 SI SI9520031A patent/SI9520031A/sl not_active IP Right Cessation
- 1995-01-24 TW TW084100605A patent/TW399059B/zh not_active IP Right Cessation
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1996
- 1996-07-29 FI FI963005A patent/FI115836B/fi not_active IP Right Cessation
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5289681A (en) * | 1976-01-22 | 1977-07-27 | Yamasa Shoyu Co Ltd | Preparation of aracytidine -5# phosphoric acid ester derivatives |
JPS552601A (en) * | 1978-06-20 | 1980-01-10 | Yamasa Shoyu Co Ltd | Anti-tumor agent for non-injection use |
WO1991012256A1 (en) * | 1990-02-09 | 1991-08-22 | Istituto Chemioterapico Italiano Fine Chemicals S.P.A. | Process for preparing l-alpha-glycerylphosphoryl-d-myoinositol and its salts |
WO1991015494A1 (en) * | 1990-03-30 | 1991-10-17 | Istituto Chemioterapico Italiano Fine Chemicals S.P.A. | Process for separating the main components of a mixture of raw deacylated phospholipids |
JPH07291982A (ja) * | 1992-06-24 | 1995-11-07 | Chemi Spa | グリセロりん脂質の製造方法 |
JPH08500345A (ja) * | 1992-08-08 | 1996-01-16 | ベーリンガー マンハイム ゲーエムベーハー | セコ‐ヌクレオシドのリポヌクレオチド、その製法及びその抗ウィルス製剤としての使用 |
JPH08512040A (ja) * | 1993-07-01 | 1996-12-17 | ベーリンガー マンハイム ゲゼルシャフト ミット ベシュレンクテル ハフツング | デオキシヌクレオシドのリポヌクレオチド、それらの製造方法および抗ウイルス薬としてのそれらの用途 |
Also Published As
Publication number | Publication date |
---|---|
DK0741740T3 (da) | 1999-10-18 |
DE59505592D1 (de) | 1999-05-12 |
PL179560B1 (pl) | 2000-09-29 |
TW399059B (en) | 2000-07-21 |
JP3609411B2 (ja) | 2005-01-12 |
FI115836B (fi) | 2005-07-29 |
WO1995020596A1 (de) | 1995-08-03 |
FI963005A0 (fi) | 1996-07-29 |
DE4402492A1 (de) | 1995-08-03 |
EP0741740B1 (de) | 1999-04-07 |
CA2181474A1 (en) | 1995-08-03 |
ES2132618T3 (es) | 1999-08-16 |
KR100242357B1 (ko) | 2000-02-01 |
ATE178610T1 (de) | 1999-04-15 |
HUT74709A (en) | 1997-02-28 |
PL315671A1 (en) | 1996-11-25 |
CA2181474C (en) | 2008-04-29 |
FI963005A (fi) | 1996-07-29 |
EP0741740A1 (de) | 1996-11-13 |
HU9602062D0 (en) | 1996-09-30 |
AU1417195A (en) | 1995-08-15 |
US5734042A (en) | 1998-03-31 |
SI9520031A (en) | 1997-04-30 |
HU222438B1 (hu) | 2003-07-28 |
BR9506654A (pt) | 1997-09-16 |
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