JP6351107B2 - チオラン骨格型糖化合物の製造方法およびチオラン骨格型糖化合物 - Google Patents
チオラン骨格型糖化合物の製造方法およびチオラン骨格型糖化合物 Download PDFInfo
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- JP6351107B2 JP6351107B2 JP2014220369A JP2014220369A JP6351107B2 JP 6351107 B2 JP6351107 B2 JP 6351107B2 JP 2014220369 A JP2014220369 A JP 2014220369A JP 2014220369 A JP2014220369 A JP 2014220369A JP 6351107 B2 JP6351107 B2 JP 6351107B2
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- alkyl group
- compound represented
- benzyloxy
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- 150000001875 compounds Chemical class 0.000 title claims description 230
- 238000004519 manufacturing process Methods 0.000 title claims description 34
- 125000001166 thiolanyl group Chemical group 0.000 title claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 126
- 125000002252 acyl group Chemical group 0.000 claims description 65
- 125000003118 aryl group Chemical group 0.000 claims description 59
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 49
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
- 238000003786 synthesis reaction Methods 0.000 claims description 41
- 230000015572 biosynthetic process Effects 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 23
- 125000005843 halogen group Chemical group 0.000 claims description 21
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 18
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 17
- 239000005450 thionucleoside Substances 0.000 claims description 16
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 125000005110 aryl thio group Chemical group 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000004104 aryloxy group Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 12
- 229910052783 alkali metal Inorganic materials 0.000 claims description 10
- 239000000543 intermediate Substances 0.000 claims description 10
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- 150000001340 alkali metals Chemical class 0.000 claims description 5
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 5
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 5
- 230000002152 alkylating effect Effects 0.000 claims description 4
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 4
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 409
- 239000000243 solution Substances 0.000 description 220
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 195
- 239000002904 solvent Substances 0.000 description 129
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 124
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 122
- 238000005160 1H NMR spectroscopy Methods 0.000 description 117
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- 239000000203 mixture Substances 0.000 description 74
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 72
- 239000012044 organic layer Substances 0.000 description 67
- 235000017557 sodium bicarbonate Nutrition 0.000 description 61
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 61
- 239000011780 sodium chloride Substances 0.000 description 61
- 229910052739 hydrogen Inorganic materials 0.000 description 57
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 56
- 229920006395 saturated elastomer Polymers 0.000 description 56
- 239000010410 layer Substances 0.000 description 54
- 238000006243 chemical reaction Methods 0.000 description 53
- -1 dibenzyl mercaptan Chemical compound 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- 238000004440 column chromatography Methods 0.000 description 42
- 0 CCOCC(C(C1*)OCC)SC1O Chemical compound CCOCC(C(C1*)OCC)SC1O 0.000 description 34
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 31
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 28
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- 239000012043 crude product Substances 0.000 description 25
- 150000003464 sulfur compounds Chemical class 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 18
- 239000007864 aqueous solution Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- 239000002994 raw material Substances 0.000 description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 12
- 150000002923 oximes Chemical class 0.000 description 12
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 11
- 239000012346 acetyl chloride Substances 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- 125000005129 aryl carbonyl group Chemical group 0.000 description 10
- 239000012230 colorless oil Substances 0.000 description 10
- 150000003462 sulfoxides Chemical class 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 150000001298 alcohols Chemical class 0.000 description 8
- 125000003277 amino group Chemical group 0.000 description 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 8
- 150000002170 ethers Chemical class 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 230000002194 synthesizing effect Effects 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 7
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 7
- 235000013877 carbamide Nutrition 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 6
- 150000003672 ureas Chemical class 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- KVQGRFRBJHIVMN-WTVRZORLSA-N [(2R,3S,4S,5R)-2-methoxy-4-phenylmethoxy-5-(phenylmethoxymethyl)thiolan-3-yl] 4-methylbenzoate Chemical compound CO[C@@H]1S[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OC(=O)c1ccc(C)cc1 KVQGRFRBJHIVMN-WTVRZORLSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000007810 chemical reaction solvent Substances 0.000 description 5
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 5
- 150000008282 halocarbons Chemical class 0.000 description 5
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000012038 nucleophile Substances 0.000 description 5
- OPAJQZNVDNZLRA-LVYZTWJOSA-N (3R,4R,5R)-3,4-dibutoxy-5-(butoxymethyl)thiolan-2-ol Chemical group CCCCOC[C@H]1SC(O)[C@H](OCCCC)[C@H]1OCCCC OPAJQZNVDNZLRA-LVYZTWJOSA-N 0.000 description 4
- OPAJQZNVDNZLRA-HJNZIYBASA-N (3R,4S,5R)-3,4-dibutoxy-5-(butoxymethyl)thiolan-2-ol Chemical group CCCCOC[C@H]1SC(O)[C@H](OCCCC)[C@@H]1OCCCC OPAJQZNVDNZLRA-HJNZIYBASA-N 0.000 description 4
- OPAJQZNVDNZLRA-WTYVYLTKSA-N (3S,4R,5R)-3,4-dibutoxy-5-(butoxymethyl)thiolan-2-ol Chemical group CCCCOC[C@H]1SC(O)[C@@H](OCCCC)[C@H]1OCCCC OPAJQZNVDNZLRA-WTYVYLTKSA-N 0.000 description 4
- UFOPUKVFDOTADY-BMHONFFRSA-N (3S,4S,5R)-2-methoxy-4-phenylmethoxy-5-(phenylmethoxymethyl)thiolan-3-ol Chemical compound COC1S[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1O UFOPUKVFDOTADY-BMHONFFRSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000002841 Lewis acid Substances 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- UAFRRAZKMJHVQZ-PVHODMMVSA-N [(2S,3S,4S)-5-oxo-1,3,4-tris(phenylmethoxy)pentan-2-yl] methanesulfonate Chemical compound CS(=O)(=O)O[C@@H](COCc1ccccc1)[C@@H](OCc1ccccc1)[C@H](OCc1ccccc1)C=O UAFRRAZKMJHVQZ-PVHODMMVSA-N 0.000 description 4
- KVQGRFRBJHIVMN-CRFRDXJISA-N [(2S,3S,4S,5R)-2-methoxy-4-phenylmethoxy-5-(phenylmethoxymethyl)thiolan-3-yl] 4-methylbenzoate Chemical compound CO[C@H]1S[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OC(=O)c1ccc(C)cc1 KVQGRFRBJHIVMN-CRFRDXJISA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229940104302 cytosine Drugs 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 150000007517 lewis acids Chemical class 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 229940095102 methyl benzoate Drugs 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- LPNBBFKOUUSUDB-UHFFFAOYSA-M p-toluate Chemical compound CC1=CC=C(C([O-])=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-M 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- KUDJXKSCDTYKFC-YESZJQIVSA-N (2R,3S,4S)-4-bromo-2,3,5-tributoxypentanal Chemical compound CCCCOC[C@H](Br)[C@@H](OCCCC)[C@@H](OCCCC)C=O KUDJXKSCDTYKFC-YESZJQIVSA-N 0.000 description 3
- UFOPUKVFDOTADY-IYWMVGAKSA-N (2R,3S,4S,5R)-2-methoxy-4-phenylmethoxy-5-(phenylmethoxymethyl)thiolan-3-ol Chemical compound CO[C@@H]1S[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1O UFOPUKVFDOTADY-IYWMVGAKSA-N 0.000 description 3
- SOWIHMANTOCUNZ-GURQWTFNSA-N (3S,4S,5S)-2-methoxy-4-phenylmethoxy-5-(phenylmethoxymethyl)oxolan-3-ol Chemical compound COC1O[C@@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1O SOWIHMANTOCUNZ-GURQWTFNSA-N 0.000 description 3
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 3
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 3
- FPIKWKVHMLYKNO-VPCXQMTMSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)-3-methylthiolan-2-yl]pyrimidin-2-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)S[C@H]1N1C(=O)N=C(N)C=C1 FPIKWKVHMLYKNO-VPCXQMTMSA-N 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- QJSPTCVRXOCBGG-ZNZIZOMTSA-N CC1=CC=C(C=C1)S(=O)(=O)O[C@@H](COCC2=CC=CC=C2)[C@H]([C@@H](C=O)F)OCC3=CC=CC=C3 Chemical compound CC1=CC=C(C=C1)S(=O)(=O)O[C@@H](COCC2=CC=CC=C2)[C@H]([C@@H](C=O)F)OCC3=CC=CC=C3 QJSPTCVRXOCBGG-ZNZIZOMTSA-N 0.000 description 3
- JHMLSHDHFVIDTI-GURQWTFNSA-N CCCCCOC[C@H]1[C@@H]([C@H](C(S1)O)OCCCCC)OCCCCC Chemical group CCCCCOC[C@H]1[C@@H]([C@H](C(S1)O)OCCCCC)OCCCCC JHMLSHDHFVIDTI-GURQWTFNSA-N 0.000 description 3
- CDFPURCGYMGVDT-ICIURTGMSA-N CCCOC[C@H]1[C@@H]([C@H](C(S1)O)OCCC)OCCC Chemical group CCCOC[C@H]1[C@@H]([C@H](C(S1)O)OCCC)OCCC CDFPURCGYMGVDT-ICIURTGMSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- BQOKAEMJGSUFRT-RRFJBIMHSA-N [(2R,3R,4R)-1,3,4-trimethoxy-5-oxopentan-2-yl] 4-methylbenzenesulfonate Chemical compound COC[C@@H](OS(=O)(=O)c1ccc(C)cc1)[C@H](OC)[C@@H](OC)C=O BQOKAEMJGSUFRT-RRFJBIMHSA-N 0.000 description 3
- KBBUVXBZDILXRB-RRFJBIMHSA-N [(2R,3R,4R)-5-oxo-1,3,4-tripropoxypentan-2-yl] methanesulfonate Chemical compound CCCOC[C@@H](OS(C)(=O)=O)[C@H](OCCC)[C@@H](OCCC)C=O KBBUVXBZDILXRB-RRFJBIMHSA-N 0.000 description 3
- RVGBTSBCXNLAOF-PVHODMMVSA-N [(2S,3S,4S)-4-methylsulfonyloxy-1-oxo-3,5-bis(phenylmethoxy)pentan-2-yl] 4-methylbenzoate Chemical compound Cc1ccc(cc1)C(=O)O[C@H](C=O)[C@H](OCc1ccccc1)[C@H](COCc1ccccc1)OS(C)(=O)=O RVGBTSBCXNLAOF-PVHODMMVSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
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- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
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- JUDDTPCJUAXYIO-OKZBNKHCSA-N [(2S,3R,4R)-1,3,4-tributoxy-5-oxopentan-2-yl] methanesulfonate Chemical compound CCCCOC[C@H](OS(C)(=O)=O)[C@H](OCCCC)[C@@H](OCCCC)C=O JUDDTPCJUAXYIO-OKZBNKHCSA-N 0.000 description 2
- JUDDTPCJUAXYIO-FGTMMUONSA-N [(2S,3R,4S)-1,3,4-tributoxy-5-oxopentan-2-yl] methanesulfonate Chemical compound CCCCOC[C@H](OS(C)(=O)=O)[C@H](OCCCC)[C@H](OCCCC)C=O JUDDTPCJUAXYIO-FGTMMUONSA-N 0.000 description 2
- JUDDTPCJUAXYIO-SQNIBIBYSA-N [(2S,3S,4S)-1,3,4-tributoxy-5-oxopentan-2-yl] methanesulfonate Chemical compound CCCCOC[C@H](OS(C)(=O)=O)[C@@H](OCCCC)[C@H](OCCCC)C=O JUDDTPCJUAXYIO-SQNIBIBYSA-N 0.000 description 2
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- 239000012045 crude solution Substances 0.000 description 2
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- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
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- FPIKWKVHMLYKNO-JJNGSOKCSA-N 4-amino-1-[(3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methylthiolan-2-yl]pyrimidin-2-one Chemical compound C[C@]1(O)[C@H](O)[C@@H](CO)SC1n1ccc(N)nc1=O FPIKWKVHMLYKNO-JJNGSOKCSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical class [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
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- KAFPKTVXDOMGLL-UHFFFAOYSA-N CCCCCOCC(CC1OCCCCC)SC1(OC)OCCCCC Chemical compound CCCCCOCC(CC1OCCCCC)SC1(OC)OCCCCC KAFPKTVXDOMGLL-UHFFFAOYSA-N 0.000 description 1
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- UZKMQYSSUQRJEE-MXEMCNAFSA-N C[C@]1([C@@H]([C@H](S[C@@H]1OC)COCC2=CC=CC=C2)OCC3=CC=CC=C3)O Chemical compound C[C@]1([C@@H]([C@H](S[C@@H]1OC)COCC2=CC=CC=C2)OCC3=CC=CC=C3)O UZKMQYSSUQRJEE-MXEMCNAFSA-N 0.000 description 1
- YIEKOPIKUBDIBE-VDEHWKIFSA-N C[C@]1([C@@H]([C@H](S[C@H]1N2C=CC(=NC2=O)N)COCC3=CC=CC=C3)OCC4=CC=CC=C4)O Chemical compound C[C@]1([C@@H]([C@H](S[C@H]1N2C=CC(=NC2=O)N)COCC3=CC=CC=C3)OCC4=CC=CC=C4)O YIEKOPIKUBDIBE-VDEHWKIFSA-N 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 238000006778 Pummerer Sulfoxide rearrangement reaction Methods 0.000 description 1
- HAUQWGSXLBQNPN-UHFFFAOYSA-N Tetrahydro-2-methylthiophen-3-ol Chemical compound CC1SCCC1O HAUQWGSXLBQNPN-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- IKIJDIYJHKUAOL-MVHAGCGSSA-N [(3S,4R,5S)-2-hydroxy-4-phenylmethoxy-5-(phenylmethoxymethyl)oxolan-3-yl] 4-methylbenzoate Chemical compound Cc1ccc(cc1)C(=O)O[C@@H]1C(O)O[C@@H](COCc2ccccc2)[C@H]1OCc1ccccc1 IKIJDIYJHKUAOL-MVHAGCGSSA-N 0.000 description 1
- VHHPDZDTKZOHTB-UHFFFAOYSA-M [Br-].[Mg+]C.C1CCOC1 Chemical compound [Br-].[Mg+]C.C1CCOC1 VHHPDZDTKZOHTB-UHFFFAOYSA-M 0.000 description 1
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- PYMYPHUHKUWMLA-WISUUJSJSA-N aldehydo-L-xylose Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WISUUJSJSA-N 0.000 description 1
- 229930195726 aldehydo-L-xylose Natural products 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- TZHXRSNHDDTXRU-UHFFFAOYSA-N benzyl 4-methylsulfonyloxypentanoate Chemical compound C(C1=CC=CC=C1)OC(CCC(C)OS(=O)(=O)C)=O TZHXRSNHDDTXRU-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- LBVNUQQORDPZCR-UHFFFAOYSA-N calcium;sulfane Chemical compound S.[Ca] LBVNUQQORDPZCR-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 150000003950 cyclic amides Chemical class 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- QENHCSSJTJWZAL-UHFFFAOYSA-N magnesium sulfide Chemical compound [Mg+2].[S-2] QENHCSSJTJWZAL-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 235000013557 nattō Nutrition 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 125000000371 nucleobase group Chemical group 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- YWWARDMVSMPOLR-UHFFFAOYSA-M oxolane;tetrabutylazanium;fluoride Chemical compound [F-].C1CCOC1.CCCC[N+](CCCC)(CCCC)CCCC YWWARDMVSMPOLR-UHFFFAOYSA-M 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- KARSJLAVUIATPJ-UHFFFAOYSA-N pentan-2-yl methanesulfonate Chemical compound CCCC(C)OS(C)(=O)=O KARSJLAVUIATPJ-UHFFFAOYSA-N 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- ZOCLAPYLSUCOGI-UHFFFAOYSA-M potassium hydrosulfide Chemical compound [SH-].[K+] ZOCLAPYLSUCOGI-UHFFFAOYSA-M 0.000 description 1
- 229940074439 potassium sodium tartrate Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000005987 sulfurization reaction Methods 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000004303 thiolan-2-yl group Chemical group [H]C1([H])SC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 125000005259 triarylamine group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/08—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/08—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to sulfur, selenium or tellurium
- C07H5/10—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to sulfur, selenium or tellurium to sulfur
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2014220369A JP6351107B2 (ja) | 2014-02-18 | 2014-10-29 | チオラン骨格型糖化合物の製造方法およびチオラン骨格型糖化合物 |
| PCT/JP2015/054306 WO2015125782A1 (fr) | 2014-02-18 | 2015-02-17 | Procédé de production d'un composé saccharidique de type à squelette de thiolane ainsi que composé saccharidique de type à squelette de thiolane |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2014029021 | 2014-02-18 | ||
| JP2014029021 | 2014-02-18 | ||
| JP2014220369A JP6351107B2 (ja) | 2014-02-18 | 2014-10-29 | チオラン骨格型糖化合物の製造方法およびチオラン骨格型糖化合物 |
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|---|---|
| JP2015172033A JP2015172033A (ja) | 2015-10-01 |
| JP6351107B2 true JP6351107B2 (ja) | 2018-07-04 |
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| JP (1) | JP6351107B2 (fr) |
| WO (1) | WO2015125782A1 (fr) |
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| CN116041308A (zh) * | 2021-07-21 | 2023-05-02 | 贵州省中国科学院天然产物化学重点实验室(贵州医科大学天然产物化学重点实验室) | 一类七元环拟糖类化合物及其制备方法和应用 |
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| JPH0925289A (ja) * | 1995-07-14 | 1997-01-28 | Yamasa Shoyu Co Ltd | ４’−チオアラビノピリミジンヌクレオシドの製造方法 |
| JPH09249690A (ja) * | 1995-07-14 | 1997-09-22 | Yamasa Shoyu Co Ltd | ４’−チオアラビノプリンヌクレオシド |
| WO1997038001A1 (fr) * | 1996-04-09 | 1997-10-16 | Yamasa Corporation | 1-(2-DESOXY-2-FLUORO-4-THIO-β-D-ARABINOFURANOSYL)CYTOSINES |
| WO1999043690A1 (fr) * | 1998-02-25 | 1999-09-02 | Rational Drug Design Laboratories | Compose de l-4'-arabinofuranonucleoside et composition medicinale le contenant |
| ES2376862T3 (es) * | 1998-07-23 | 2012-03-20 | Southern Research Institute | Utilización de compuestos de tioarabinofuranosilo |
| WO2001066118A1 (fr) * | 2000-03-08 | 2001-09-13 | Southern Research Institute | Nucleosides 4'-thio-l-xylo furanosyle, precurseurs de ces derniers et procedes de preparation et d'utilisation associes |
| TWI247609B (en) * | 2001-01-23 | 2006-01-21 | Nihon Mediphysics Co Ltd | Agent for diagnosis of tissue proliferation activity or the treatment of proliferative disease |
| JP4651942B2 (ja) * | 2001-12-20 | 2011-03-16 | フアーマセツト・インコーポレイテッド | Ｅｂｖ及びｋｈｓｖ感染並びにそれに伴う異常細胞増殖の治療 |
| AU2003256619A1 (en) * | 2002-07-24 | 2004-02-09 | Isis Pharmaceuticals, Inc. | Pyrrolopyrimidine thionucleoside analogs as antivirals |
| JP2006335737A (ja) * | 2005-06-03 | 2006-12-14 | Ihara Nikkei Kagaku Kogyo Kk | ベンゾ［ｃ］ヘテロ５員環化合物の製造方法 |
| TWI476204B (zh) * | 2009-12-18 | 2015-03-11 | Libramedicina Inc | 製備經取代之１－Ｏ－醯基－２－脫氧－２－氟－４－硫－β－Ｄ－阿拉伯呋喃糖的製程 |
| DK2883866T3 (da) * | 2012-08-13 | 2019-05-13 | Fujifilm Corp | MELLEMPRODUKT TIL SYNTESE AF 1-(2-DEOXY-2-FLUOR-4-THIO-beta-D- ARABINOFURANOSYL)CYTOSIN, MELLEMPRODUKT TIL SYNTESE AF THIONUKLEOSID OG FREMGANGSMÅDER TIL FREMSTILLING AF DISSE MELLEMPRODUKTER |
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