JPH0427991B2 - - Google Patents

Info

Publication number: JPH0427991B2
Authority: JP; Japan
Prior art keywords: compound; reaction; oar; lial; group
Prior art date: 1983-03-09
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

Application number

JP3725883A

Other languages

English (en)

Japanese (ja)

Other versions

JPS59163397A (ja

Inventor

Ryoji Noyori

Yoshihiro Hayakawa

Yoshio Aso

Mamoru Uchama

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.)

Seikagaku Corp

Original Assignee

Seikagaku Corp

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.)

1983-03-09

Filing date

1983-03-09

Publication date

1992-05-13

1983-03-09 Application filed by Seikagaku Corp filed Critical Seikagaku Corp

1983-03-09 Priority to JP3725883A priority Critical patent/JPS59163397A/ja

1984-09-14 Publication of JPS59163397A publication Critical patent/JPS59163397A/ja

1992-05-13 Publication of JPH0427991B2 publication Critical patent/JPH0427991B2/ja

Status Granted legal-status Critical Current

Links

-1 aluminum compound Chemical class 0.000 claims description 44
239000002777 nucleoside Substances 0.000 claims description 44
238000006243 chemical reaction Methods 0.000 claims description 41
239000003795 chemical substances by application Substances 0.000 claims description 29
150000003833 nucleoside derivatives Chemical class 0.000 claims description 27
229910010199 LiAl Inorganic materials 0.000 claims description 24
230000000865 phosphorylative effect Effects 0.000 claims description 24
150000001875 compounds Chemical class 0.000 claims description 21
229910052782 aluminium Inorganic materials 0.000 claims description 20
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 13
239000000203 mixture Substances 0.000 claims description 11
239000007795 chemical reaction product Substances 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
239000002904 solvent Substances 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
229910052698 phosphorus Inorganic materials 0.000 claims description 2
239000011574 phosphorus Substances 0.000 claims description 2
229940126062 Compound A Drugs 0.000 claims 1
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims 1
101100109871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) aro-8 gene Proteins 0.000 claims 1
239000002253 acid Substances 0.000 claims 1
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
239000000243 solution Substances 0.000 description 40
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 40
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
238000003786 synthesis reaction Methods 0.000 description 23
238000000034 method Methods 0.000 description 22
230000015572 biosynthetic process Effects 0.000 description 21
239000000460 chlorine Substances 0.000 description 20
238000005481 NMR spectroscopy Methods 0.000 description 19
239000011541 reaction mixture Substances 0.000 description 18
238000003756 stirring Methods 0.000 description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
239000000047 product Substances 0.000 description 14
239000010410 layer Substances 0.000 description 13
125000003835 nucleoside group Chemical group 0.000 description 13
238000005269 aluminizing Methods 0.000 description 10
229910052744 lithium Inorganic materials 0.000 description 10
238000006366 phosphorylation reaction Methods 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
YQNQTEBHHUSESQ-UHFFFAOYSA-N lithium aluminate Chemical compound [Li+].[O-][Al]=O YQNQTEBHHUSESQ-UHFFFAOYSA-N 0.000 description 9
230000026731 phosphorylation Effects 0.000 description 8
239000000126 substance Substances 0.000 description 8
ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 7
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 7
229910019142 PO4 Inorganic materials 0.000 description 7
239000012267 brine Substances 0.000 description 7
239000010452 phosphate Substances 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N CHCl3 Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
RWQNBRDOKXIBIV-UHFFFAOYSA-N Thymine Natural products CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 6
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Natural products O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 5
125000001309 chloro group Chemical group Cl* 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000006260 foam Substances 0.000 description 5
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
HGLRBQHXIBHZTD-QJPTWQEYSA-N (2r,3s,5r)-5-(6-aminopurin-9-yl)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-3-ol Chemical compound C1[C@H](O)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 HGLRBQHXIBHZTD-QJPTWQEYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 4
238000010494 dissociation reaction Methods 0.000 description 4
230000005593 dissociations Effects 0.000 description 4
239000004210 ether based solvent Substances 0.000 description 4
239000000284 extract Substances 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
239000002773 nucleotide Substances 0.000 description 4
125000003729 nucleotide group Chemical group 0.000 description 4
125000004430 oxygen atom Chemical group O* 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 3
229930024421 Adenine Natural products 0.000 description 3
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
230000004913 activation Effects 0.000 description 3
229960000643 adenine Drugs 0.000 description 3
150000004645 aluminates Chemical class 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
125000001369 canonical nucleoside group Chemical group 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000010353 genetic engineering Methods 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 3
230000035484 reaction time Effects 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
229940113082 thymine Drugs 0.000 description 3
229940035893 uracil Drugs 0.000 description 3
238000005406 washing Methods 0.000 description 3
GFDUSNQQMOENLR-UHFFFAOYSA-N 2',3'-O-Isopropylidene-Uridine Natural products C12OC(C)(C)OC2C(CO)OC1N1C=CC(=O)NC1=O GFDUSNQQMOENLR-UHFFFAOYSA-N 0.000 description 2
SEYILVDPIQPEAP-HBNTYKKESA-N 2-amino-9-[(2r,4s,5r)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-hydroxyoxolan-2-yl]-3h-purin-6-one Chemical compound C1[C@H](O)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@H]1N1C(NC(N)=NC2=O)=C2N=C1 SEYILVDPIQPEAP-HBNTYKKESA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
108091034117 Oligonucleotide Proteins 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
229910018540 Si C Inorganic materials 0.000 description 2
238000007792 addition Methods 0.000 description 2
239000003905 agrochemical Substances 0.000 description 2
150000004703 alkoxides Chemical class 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
ITVPBBDAZKBMRP-UHFFFAOYSA-N chloro-dioxido-oxo-$l^{5}-phosphane;hydron Chemical compound OP(O)(Cl)=O ITVPBBDAZKBMRP-UHFFFAOYSA-N 0.000 description 2
229940104302 cytosine Drugs 0.000 description 2
239000005549 deoxyribonucleoside Substances 0.000 description 2
FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 2
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000012039 electrophile Substances 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
238000000434 field desorption mass spectrometry Methods 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
239000007789 gas Substances 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
239000012046 mixed solvent Substances 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
108020004707 nucleic acids Proteins 0.000 description 2
102000039446 nucleic acids Human genes 0.000 description 2
150000007523 nucleic acids Chemical class 0.000 description 2
239000012038 nucleophile Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
230000009257 reactivity Effects 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
229910001220 stainless steel Inorganic materials 0.000 description 2
239000010935 stainless steel Substances 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
OABKEGPGBFWYDX-UHFFFAOYSA-N (2,4-dinitrophenyl) dihydrogen phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O OABKEGPGBFWYDX-UHFFFAOYSA-N 0.000 description 1
UBGDNZQSYVIVHU-PEBGCTIMSA-N 1-[(3ar,4r,6r,6ar)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-4-aminopyrimidin-2-one Chemical compound N1([C@@H]2O[C@H](CO)[C@H]3OC(O[C@H]32)(C)C)C=CC(N)=NC1=O UBGDNZQSYVIVHU-PEBGCTIMSA-N 0.000 description 1
GFDUSNQQMOENLR-PEBGCTIMSA-N 1-[(3ar,4r,6r,6ar)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]pyrimidine-2,4-dione Chemical compound N1([C@@H]2O[C@H](CO)[C@H]3OC(O[C@H]32)(C)C)C=CC(=O)NC1=O GFDUSNQQMOENLR-PEBGCTIMSA-N 0.000 description 1
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 1
XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
JPOUAPFYUWXKLK-DMDPSCGWSA-N 4-amino-1-[(2r,4s,5r)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-4-hydroxyoxolan-2-yl]pyrimidin-2-one Chemical compound C1[C@H](O)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 JPOUAPFYUWXKLK-DMDPSCGWSA-N 0.000 description 1
BOFRXDMCQRTGII-UHFFFAOYSA-N 619-08-9 Chemical compound OC1=CC=C([N+]([O-])=O)C=C1Cl BOFRXDMCQRTGII-UHFFFAOYSA-N 0.000 description 1
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
229910018509 Al—N Inorganic materials 0.000 description 1
229910018516 Al—O Inorganic materials 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
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 1
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
LCCLUOXEZAHUNS-WOUKDFQISA-N [(3ar,4r,6r,6ar)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]1O[C@H](CO)[C@H]2OC(C)(C)O[C@H]21 LCCLUOXEZAHUNS-WOUKDFQISA-N 0.000 description 1
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 description 1
NGFFLHMFSINFGB-UHFFFAOYSA-N [chloro(methoxy)phosphoryl]oxymethane Chemical compound COP(Cl)(=O)OC NGFFLHMFSINFGB-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
229950006790 adenosine phosphate Drugs 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
HYGYSIDIKIGPJA-UHFFFAOYSA-N chloroform;ethyl acetate;methanol Chemical compound OC.ClC(Cl)Cl.CCOC(C)=O HYGYSIDIKIGPJA-UHFFFAOYSA-N 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
238000011161 development Methods 0.000 description 1
229920001971 elastomer Polymers 0.000 description 1
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
150000004676 glycans Chemical class 0.000 description 1
229930182470 glycoside Natural products 0.000 description 1
150000002338 glycosides Chemical class 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
125000005462 imide group Chemical group 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
IKQSNKKSCOCCOD-UHFFFAOYSA-N molport-028-600-099 Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1Cl IKQSNKKSCOCCOD-UHFFFAOYSA-N 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
229920001542 oligosaccharide Polymers 0.000 description 1
150000002482 oligosaccharides Chemical class 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
108091033319 polynucleotide Proteins 0.000 description 1
102000040430 polynucleotide Human genes 0.000 description 1
239000002157 polynucleotide Substances 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000011002 quantification Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
239000002342 ribonucleoside Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
150000003458 sulfonic acid derivatives Chemical class 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1

Landscapes

Saccharide Compounds (AREA)

JP3725883A 1983-03-09 1983-03-09 リン酸化合物の製造方法 Granted JPS59163397A (ja)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
JP3725883A JPS59163397A (ja)	1983-03-09	1983-03-09	リン酸化合物の製造方法

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP3725883A JPS59163397A (ja)	1983-03-09	1983-03-09	リン酸化合物の製造方法

Publications (2)

Publication Number	Publication Date
JPS59163397A JPS59163397A (ja)	1984-09-14
JPH0427991B2 true JPH0427991B2 (fr)	1992-05-13

Family

ID=12492622

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP3725883A Granted JPS59163397A (ja)	1983-03-09	1983-03-09	リン酸化合物の製造方法

Country Status (1)

Country	Link
JP (1)	JPS59163397A (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TW279165B (fr) *	1992-07-08	1996-06-21	Takeda Pharm Industry Co Ltd

1983
- 1983-03-09 JP JP3725883A patent/JPS59163397A/ja active Granted

Also Published As

Publication number	Publication date
JPS59163397A (ja)	1984-09-14

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US6998484B2 (en)	2006-02-14	Synthesis of purine locked nucleic acid analogues
US4959463A (en)	1990-09-25	Intermediates
EP3004131B1 (fr)	2020-07-22	Blocs de construction à base de phosphoramidite pour oligonucléotides conjugués à des sucres
JPH06199888A (ja)	1994-07-19	ヌクレオシド誘導体
JP2004536125A (ja)	2004-12-02	Ｌｎａホスホラミダイトの製造法
JPH07103150B2 (ja)	1995-11-08	２’―０―アルキルヌクレオチド並びにこのようなヌクレオチドを含むポリマー
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JPH0427991B2 (fr)	1992-05-13
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WO2005070946A1 (fr)	2005-08-04	Compose d'acide ribonucleique et procede de synthese en phase liquide de compose d'acide oligonucleique
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JPS6270392A (ja)	1987-03-31	オリゴヌクレオチド化合物の製造法
JPS6025439B2 (ja)	1985-06-18	５′−ヌクレオチドの製造法