OA10349A - Processes for the diastereoselective synthesis of nucleosides - Google Patents

Processes for the diastereoselective synthesis of nucleosides Download PDF

Info

Publication number: OA10349A
Authority: OA; OAPI
Prior art keywords: oxathiolane; carboxylate; menthyl; formula; cis
Prior art date: 1993-06-07

Application number

OA60438A

Other languages

English (en)

Inventor

Tarek Mansour

Haolun Jin

Allan H L Tse

M Arshad Siddiqui

Original Assignee

Iaf Biochem Int

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.)

1993-06-07

Filing date

1993-11-19

Publication date

2001-10-18

1993-11-19 Application filed by Iaf Biochem Int filed Critical Iaf Biochem Int

2001-10-18 Publication of OA10349A publication Critical patent/OA10349A/en

Links

238000000034 method Methods 0.000 title claims abstract description 76
230000008569 process Effects 0.000 title claims abstract description 52
239000002777 nucleoside Substances 0.000 title claims description 42
125000003835 nucleoside group Chemical group 0.000 title description 16
238000003786 synthesis reaction Methods 0.000 title description 11
230000015572 biosynthetic process Effects 0.000 title description 9
229910052717 sulfur Inorganic materials 0.000 claims abstract description 46
229910052736 halogen Chemical group 0.000 claims abstract description 15
229940127073 nucleoside analogue Drugs 0.000 claims abstract description 9
239000000203 mixture Substances 0.000 claims description 106
150000001875 compounds Chemical class 0.000 claims description 46
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 34
-1 bromo,chloro, iodo Chemical group 0.000 claims description 30
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 30
229920006395 saturated elastomer Polymers 0.000 claims description 30
KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 26
125000000217 alkyl group Chemical group 0.000 claims description 26
230000002829 reductive effect Effects 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 19
IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 claims description 19
239000002841 Lewis acid Substances 0.000 claims description 18
125000003118 aryl group Chemical group 0.000 claims description 18
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 18
150000007517 lewis acids Chemical class 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 13
229910052739 hydrogen Inorganic materials 0.000 claims description 13
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 11
229940041616 menthol Drugs 0.000 claims description 11
SFLGIMGLWCVAHP-UHFFFAOYSA-N 5h-oxathiole Chemical compound C1OSC=C1 SFLGIMGLWCVAHP-UHFFFAOYSA-N 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
125000003710 aryl alkyl group Chemical group 0.000 claims description 8
229940104302 cytosine Drugs 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 7
125000002252 acyl group Chemical group 0.000 claims description 6
XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
150000002148 esters Chemical class 0.000 claims description 5
XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 claims description 5
229960004413 flucytosine Drugs 0.000 claims description 5
230000001279 glycosylating effect Effects 0.000 claims description 5
125000005389 trialkylsiloxy group Chemical group 0.000 claims description 5
125000004665 trialkylsilyl group Chemical group 0.000 claims description 5
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
125000004104 aryloxy group Chemical group 0.000 claims description 4
150000004820 halides Chemical class 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
150000003212 purines Chemical class 0.000 claims description 4
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 4
WOFYIEFGBZDLOT-GSVOUGTGSA-N O[C@H]1CCS(C(O)=O)O1 Chemical compound O[C@H]1CCS(C(O)=O)O1 WOFYIEFGBZDLOT-GSVOUGTGSA-N 0.000 claims description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 3
BFAKENXZKHGIGE-UHFFFAOYSA-N bis(2,3,5,6-tetrafluoro-4-iodophenyl)diazene Chemical compound FC1=C(C(=C(C(=C1F)I)F)F)N=NC1=C(C(=C(C(=C1F)F)I)F)F BFAKENXZKHGIGE-UHFFFAOYSA-N 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 2
LCDCPQHFCOBUEF-UHFFFAOYSA-N pyrrolidine-1-carboxamide Chemical compound NC(=O)N1CCCC1 LCDCPQHFCOBUEF-UHFFFAOYSA-N 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims 15
125000001246 bromo group Chemical group Br* 0.000 claims 12
125000001309 chloro group Chemical group Cl* 0.000 claims 12
125000002346 iodo group Chemical group I* 0.000 claims 9
101100001677 Emericella variicolor andL gene Proteins 0.000 claims 6
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 6
DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 claims 2
NZAMMJKYTYHSHN-UHFFFAOYSA-N trimethyl-[(2-methyl-1,3-oxathiolan-5-yl)methyl]azanium Chemical compound CC1OC(C[N+](C)(C)C)CS1 NZAMMJKYTYHSHN-UHFFFAOYSA-N 0.000 claims 2
DLNKOYKMWOXYQA-VXNVDRBHSA-N (+)-norephedrine Chemical compound C[C@@H](N)[C@@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-VXNVDRBHSA-N 0.000 claims 1
DLNKOYKMWOXYQA-CBAPKCEASA-N (-)-norephedrine Chemical compound C[C@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-CBAPKCEASA-N 0.000 claims 1
SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 claims 1
150000001298 alcohols Chemical class 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims 1
150000002367 halogens Chemical group 0.000 abstract description 14
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 abstract description 2
229910052760 oxygen Inorganic materials 0.000 abstract description 2
125000002619 bicyclic group Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 212
239000000243 solution Substances 0.000 description 81
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 67
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 53
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 43
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 42
238000005481 NMR spectroscopy Methods 0.000 description 41
239000007787 solid Substances 0.000 description 41
239000000725 suspension Substances 0.000 description 37
239000000047 product Substances 0.000 description 35
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
239000002904 solvent Substances 0.000 description 29
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
239000012267 brine Substances 0.000 description 24
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
229910001868 water Inorganic materials 0.000 description 23
BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 22
229910052786 argon Inorganic materials 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 21
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
239000012043 crude product Substances 0.000 description 18
238000003756 stirring Methods 0.000 description 18
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
239000000463 material Substances 0.000 description 16
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 14
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 14
229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
150000003833 nucleoside derivatives Chemical class 0.000 description 12
235000017557 sodium bicarbonate Nutrition 0.000 description 12
AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-Me3C6H3 Natural products CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 11
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
239000012074 organic phase Substances 0.000 description 11
239000003208 petroleum Substances 0.000 description 11
239000007858 starting material Substances 0.000 description 11
235000000346 sugar Nutrition 0.000 description 11
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 10
238000005160 1H NMR spectroscopy Methods 0.000 description 10
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 10
WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 10
125000004432 carbon atom Chemical group C* 0.000 description 10
238000001640 fractional crystallisation Methods 0.000 description 10
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 9
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
229960004132 diethyl ether Drugs 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
229960001866 silicon dioxide Drugs 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 8
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
239000000543 intermediate Substances 0.000 description 8
229910052740 iodine Inorganic materials 0.000 description 8
239000012071 phase Substances 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
239000002002 slurry Substances 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 7
150000007942 carboxylates Chemical class 0.000 description 7
239000003638 chemical reducing agent Substances 0.000 description 7
239000000460 chlorine Substances 0.000 description 7
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 7
229940011051 isopropyl acetate Drugs 0.000 description 7
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 7
239000010410 layer Substances 0.000 description 7
229960001407 sodium bicarbonate Drugs 0.000 description 7
229960003010 sodium sulfate Drugs 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 7
229940124024 weight reducing agent Drugs 0.000 description 7
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical class C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 6
125000004429 atom Chemical group 0.000 description 6
229910052794 bromium Inorganic materials 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
238000001914 filtration Methods 0.000 description 6
230000003287 optical effect Effects 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
238000010898 silica gel chromatography Methods 0.000 description 6
235000019345 sodium thiosulphate Nutrition 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
238000003828 vacuum filtration Methods 0.000 description 6
NOOLISFMXDJSKH-AEJSXWLSSA-N (+)-menthol Chemical compound CC(C)[C@H]1CC[C@H](C)C[C@@H]1O NOOLISFMXDJSKH-AEJSXWLSSA-N 0.000 description 5
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 description 5
NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
238000011065 in-situ storage Methods 0.000 description 5
239000012280 lithium aluminium hydride Substances 0.000 description 5
229940001474 sodium thiosulfate Drugs 0.000 description 5
PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
238000005361 D2 NMR spectroscopy Methods 0.000 description 4
IJCKBIINTQEGLY-UHFFFAOYSA-N N(4)-acetylcytosine Chemical compound CC(=O)NC1=CC=NC(=O)N1 IJCKBIINTQEGLY-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
125000003342 alkenyl group Chemical group 0.000 description 4
125000000304 alkynyl group Chemical group 0.000 description 4
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
HXJFQNUWPUICNY-UHFFFAOYSA-N disiamylborane Chemical compound CC(C)C(C)BC(C)C(C)C HXJFQNUWPUICNY-UHFFFAOYSA-N 0.000 description 4
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
229960004873 levomenthol Drugs 0.000 description 4
229940073584 methylene chloride Drugs 0.000 description 4
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
239000003921 oil Substances 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 4
IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 3
WJJSZTJGFCFNKI-UHFFFAOYSA-N 1,3-oxathiolane Chemical class C1CSCO1 WJJSZTJGFCFNKI-UHFFFAOYSA-N 0.000 description 3
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 3
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
ILYXXUBAZBRPLA-UHFFFAOYSA-N [O-]C([S+]1OCCC1)=O Chemical compound [O-]C([S+]1OCCC1)=O ILYXXUBAZBRPLA-UHFFFAOYSA-N 0.000 description 3
230000010933 acylation Effects 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
230000004075 alteration Effects 0.000 description 3
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000003480 eluent Substances 0.000 description 3
AZLPEJUVWWGLHA-UHFFFAOYSA-N ethyl acetate;hexane;methanol Chemical compound OC.CCCCCC.CCOC(C)=O AZLPEJUVWWGLHA-UHFFFAOYSA-N 0.000 description 3
238000003818 flash chromatography Methods 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
230000013595 glycosylation Effects 0.000 description 3
238000006206 glycosylation reaction Methods 0.000 description 3
HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 3
239000012456 homogeneous solution Substances 0.000 description 3
239000011630 iodine Substances 0.000 description 3
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 3
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical compound C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 description 3
238000010992 reflux Methods 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
235000002639 sodium chloride Nutrition 0.000 description 3
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000000758 substrate Substances 0.000 description 3
150000003573 thiols Chemical class 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
229940035893 uracil Drugs 0.000 description 3
WTHKEDIFIXHRRL-UHFFFAOYSA-N 1,3-oxathiolan-2-yl acetate Chemical compound CC(=O)OC1OCCS1 WTHKEDIFIXHRRL-UHFFFAOYSA-N 0.000 description 2
WURYWHAKEJHAOV-UHFFFAOYSA-N 2,5-dihydrothiophene Chemical class C1SCC=C1 WURYWHAKEJHAOV-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
241000598436 Human T-cell lymphotropic virus Species 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000000840 anti-viral effect Effects 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
229960004217 benzyl alcohol Drugs 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
239000013058 crude material Substances 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
239000000539 dimer Substances 0.000 description 2
235000019439 ethyl acetate Nutrition 0.000 description 2
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
150000002431 hydrogen Chemical class 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
239000000376 reactant Substances 0.000 description 2
239000012047 saturated solution Substances 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
229960002668 sodium chloride Drugs 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
238000000967 suction filtration Methods 0.000 description 2
125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 2
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
238000005406 washing Methods 0.000 description 2
239000008096 xylene Substances 0.000 description 2
239000001677 (2R,5R)-1,4-dithiane-2,5-diol Substances 0.000 description 1
WRUGSNIJLUOGQF-INEUFUBQSA-N (2r,5r)-5-acetyloxy-1,3-oxathiolane-2-carboxylic acid Chemical compound CC(=O)O[C@H]1CS[C@H](C(O)=O)O1 WRUGSNIJLUOGQF-INEUFUBQSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
150000004865 1,3-dithiolanes Chemical class 0.000 description 1
FYAVYWUBPQMCQN-UHFFFAOYSA-N 1,3-oxathiolan-5-one Chemical class O=C1CSCO1 FYAVYWUBPQMCQN-UHFFFAOYSA-N 0.000 description 1
YUIOPHXTILULQC-UHFFFAOYSA-N 1,4-Dithiane-2,5-diol Chemical compound OC1CSC(O)CS1 YUIOPHXTILULQC-UHFFFAOYSA-N 0.000 description 1
UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 description 1
NDVMCQUOSYOQMZ-UHFFFAOYSA-N 2,2-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)C(C(N)=O)[Si](C)(C)C NDVMCQUOSYOQMZ-UHFFFAOYSA-N 0.000 description 1
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
YQBLQKZERMAVDO-UHFFFAOYSA-N 2-oxo-2-phenylacetaldehyde;hydrate Chemical compound O.O=CC(=O)C1=CC=CC=C1 YQBLQKZERMAVDO-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
FLJWVVUJGVNXMZ-UHFFFAOYSA-N 2-sulfanylacetaldehyde Chemical compound SCC=O FLJWVVUJGVNXMZ-UHFFFAOYSA-N 0.000 description 1
GIIGHSIIKVOWKZ-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidine Chemical class N1=CN=CC2=NNN=C21 GIIGHSIIKVOWKZ-UHFFFAOYSA-N 0.000 description 1
SMAFZAIZBGJCRN-UHFFFAOYSA-N 5,6-bis(trimethylsilyl)-1h-pyrimidine-2,4-dione Chemical compound C[Si](C)(C)C=1NC(=O)NC(=O)C=1[Si](C)(C)C SMAFZAIZBGJCRN-UHFFFAOYSA-N 0.000 description 1
MFEFTTYGMZOIKO-UHFFFAOYSA-N 5-azacytosine Chemical compound NC1=NC=NC(=O)N1 MFEFTTYGMZOIKO-UHFFFAOYSA-N 0.000 description 1
LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
CODYSRJDEULAFH-UHFFFAOYSA-N 5-oxo-1,3-oxathiolane-2-carboxylic acid Chemical compound OC(=O)C1OC(=O)CS1 CODYSRJDEULAFH-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
125000003860 C1-C20 alkoxy group Chemical group 0.000 description 1
BLCUFORXSIYEPS-UHFFFAOYSA-N CC(OC(CC1)O[S+]1C([O-])=O)=O Chemical compound CC(OC(CC1)O[S+]1C([O-])=O)=O BLCUFORXSIYEPS-UHFFFAOYSA-N 0.000 description 1
UAXPUZXLRGNAMU-UHFFFAOYSA-N CCOC([S+](CC1)OC1OC(C)=O)=O Chemical compound CCOC([S+](CC1)OC1OC(C)=O)=O UAXPUZXLRGNAMU-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
241000700721 Hepatitis B virus Species 0.000 description 1
206010061598 Immunodeficiency Diseases 0.000 description 1
208000029462 Immunodeficiency disease Diseases 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
101100391171 Schizosaccharomyces pombe (strain 972 / ATCC 24843) for3 gene Proteins 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
241000700605 Viruses Species 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
JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 1
OEGAMYZOUWNLEO-UHFFFAOYSA-N [butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CCCC[Si](C)(C)OS(=O)(=O)C(F)(F)F OEGAMYZOUWNLEO-UHFFFAOYSA-N 0.000 description 1
LJJVEZISMNEQRE-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate;[dimethyl-(trimethylsilylamino)silyl]methane Chemical compound C[Si](C)(C)N[Si](C)(C)C.CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F LJJVEZISMNEQRE-UHFFFAOYSA-N 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000036436 anti-hiv Effects 0.000 description 1
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000004296 chiral HPLC Methods 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
239000013078 crystal Substances 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
HKDDTBNGYXIRJP-UHFFFAOYSA-N cyclohexane;2-methoxy-2-methylpropane Chemical compound COC(C)(C)C.C1CCCCC1 HKDDTBNGYXIRJP-UHFFFAOYSA-N 0.000 description 1
238000006392 deoxygenation reaction Methods 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
BAQKJENAVQLANS-UHFFFAOYSA-N fenbutrazate Chemical compound C=1C=CC=CC=1C(CC)C(=O)OCCN(C1C)CCOC1C1=CC=CC=C1 BAQKJENAVQLANS-UHFFFAOYSA-N 0.000 description 1
229960002533 fenbutrazate Drugs 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000005227 gel permeation chromatography Methods 0.000 description 1
238000007429 general method Methods 0.000 description 1
125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
230000007813 immunodeficiency Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
SPAKMVQVTSVXES-UHFFFAOYSA-N methanol;oxolane;hydrate Chemical compound O.OC.C1CCOC1 SPAKMVQVTSVXES-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000000178 monomer Substances 0.000 description 1
RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
ORQWTLCYLDRDHK-UHFFFAOYSA-N phenylselanylbenzene Chemical compound C=1C=CC=CC=1[Se]C1=CC=CC=C1 ORQWTLCYLDRDHK-UHFFFAOYSA-N 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
ZIJTYIRGFVHPHZ-UHFFFAOYSA-N selenium oxide(seo) Chemical group [Se]=O ZIJTYIRGFVHPHZ-UHFFFAOYSA-N 0.000 description 1
229910000077 silane Inorganic materials 0.000 description 1
SRRKNRDXURUMPP-UHFFFAOYSA-N sodium disulfide Chemical compound [Na+].[Na+].[S-][S-] SRRKNRDXURUMPP-UHFFFAOYSA-N 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000007944 thiolates Chemical class 0.000 description 1
229940113082 thymine Drugs 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
WRTMQOHKMFDUKX-UHFFFAOYSA-N triiodide Chemical compound I[I-]I WRTMQOHKMFDUKX-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
125000004417 unsaturated alkyl group Chemical group 0.000 description 1
230000003313 weakening effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D411/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D497/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D497/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D497/08—Bridged systems

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Health & Medical Sciences (AREA)
Oncology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Virology (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Communicable Diseases (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)

OA60438A 1993-06-07 1993-11-19 Processes for the diastereoselective synthesis of nucleosides OA10349A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB939311709A GB9311709D0 (en)	1993-06-07	1993-06-07	Stereoselective synthesis of nucleoside analogues using bicycle intermediate

Publications (1)

Publication Number	Publication Date
OA10349A true OA10349A (en)	2001-10-18

Family

ID=10736757

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA60438A OA10349A (en)	1993-06-07	1993-11-19	Processes for the diastereoselective synthesis of nucleosides

Country Status (21)

Country	Link
US (1)	US5763606A (de)
EP (1)	EP0654031B1 (de)
JP (1)	JP3110461B2 (de)
KR (1)	KR100304072B1 (de)
CN (1)	CN1046720C (de)
AT (1)	ATE188215T1 (de)
AU (1)	AU668829B2 (de)
BR (1)	BR9405423A (de)
CA (1)	CA2141029C (de)
DE (1)	DE69422374T2 (de)
DK (1)	DK0654031T3 (de)
ES (1)	ES2139744T3 (de)
FI (1)	FI112078B (de)
GB (1)	GB9311709D0 (de)
HU (1)	HU219199B (de)
NO (1)	NO303449B1 (de)
NZ (1)	NZ267379A (de)
OA (1)	OA10349A (de)
PL (1)	PL180870B1 (de)
RU (1)	RU2139870C1 (de)
WO (1)	WO1994029301A1 (de)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6175008B1 (en) *	1988-04-11	2001-01-16	Biochem Pharma Inc.	Processes for preparing substituted 1,3-oxathiolanes with antiviral properties
US6034087A (en) *	1994-10-22	2000-03-07	Chong Kun Dang Corp.	Nucleoside derivatives and process for preparing thereof
JP4249393B2 (ja)	1998-08-12	2009-04-02	トライアングル・ファーマシューティカルズ，インコーポレイテッド	１，３−オキサチオランヌクレオチドの製造方法
US6979561B1 (en)	1998-10-09	2005-12-27	Gilead Sciences, Inc.	Non-homogeneous systems for the resolution of enantiomeric mixtures
CA2308559C (en)	2000-05-16	2005-07-26	Brantford Chemicals Inc.	1,3-oxathiolan-5-ones useful in the production of antiviral nucleoside analogues
PT1574512E (pt)	2001-03-01	2008-03-05	Abbott Lab	Formas polimórficas e outras formas cristalinas de cis-ftc
EA015145B1 (ru)	2003-01-14	2011-06-30	Джилид Сайэнс, Инк.	Фармацевтическая композиция и пероральная фармацевтическая дозированная форма (варианты), проявляющие активность в отношении вич-инфекций, лечебный набор и таблетка и способ лечения или предотвращения симптомов или эффектов вич-инфекции
CN101044122A (zh) *	2004-02-03	2007-09-26	埃莫里大学	制备1,3－二氧戊环核苷的方法
TWI375560B (en)	2005-06-13	2012-11-01	Gilead Sciences Inc	Composition comprising dry granulated emtricitabine and tenofovir df and method for making the same
TWI471145B (zh)	2005-06-13	2015-02-01	Bristol Myers Squibb & Gilead Sciences Llc	單一式藥學劑量型

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5047407A (en) *	1989-02-08	1991-09-10	Iaf Biochem International, Inc.	2-substituted-5-substituted-1,3-oxathiolanes with antiviral properties
US5204466A (en) *	1990-02-01	1993-04-20	Emory University	Method and compositions for the synthesis of bch-189 and related compounds
GB9009861D0 (en) *	1990-05-02	1990-06-27	Glaxo Group Ltd	Chemical compounds
AU9125991A (en) *	1990-12-05	1992-07-08	University Of Georgia Research Foundation, Inc., The	Enantiomerically pure beta -l-(-)-1,3-oxathiolane nucleosides
ZA923641B (en) *	1991-05-21	1993-02-24	Iaf Biochem Int	Processes for the diastereoselective synthesis of nucleosides
GB9116601D0 (en) *	1991-08-01	1991-09-18	Iaf Biochem Int	1,3-oxathiolane nucleoside analogues
US5332814A (en) *	1991-11-12	1994-07-26	Ciba-Geigy Corporation	Process for the preparation of carbacyclic nucleosides, and intermediates

1993
- 1993-06-07 GB GB939311709A patent/GB9311709D0/en active Pending
- 1993-11-19 OA OA60438A patent/OA10349A/en unknown
1994
- 1994-06-07 WO PCT/CA1994/000311 patent/WO1994029301A1/en not_active Ceased
- 1994-06-07 BR BR9405423A patent/BR9405423A/pt not_active Application Discontinuation
- 1994-06-07 EP EP94918252A patent/EP0654031B1/de not_active Expired - Lifetime
- 1994-06-07 DK DK94918252T patent/DK0654031T3/da active
- 1994-06-07 PL PL94307350A patent/PL180870B1/pl not_active IP Right Cessation
- 1994-06-07 JP JP07501139A patent/JP3110461B2/ja not_active Expired - Fee Related
- 1994-06-07 ES ES94918252T patent/ES2139744T3/es not_active Expired - Lifetime
- 1994-06-07 CN CN94190356A patent/CN1046720C/zh not_active Expired - Fee Related
- 1994-06-07 CA CA002141029A patent/CA2141029C/en not_active Expired - Fee Related
- 1994-06-07 HU HU9500364A patent/HU219199B/hu not_active IP Right Cessation
- 1994-06-07 US US08/379,644 patent/US5763606A/en not_active Expired - Fee Related
- 1994-06-07 RU RU95108553A patent/RU2139870C1/ru not_active IP Right Cessation
- 1994-06-07 DE DE69422374T patent/DE69422374T2/de not_active Expired - Fee Related
- 1994-06-07 NZ NZ267379A patent/NZ267379A/en not_active IP Right Cessation
- 1994-06-07 AT AT94918252T patent/ATE188215T1/de not_active IP Right Cessation
- 1994-06-07 AU AU69667/94A patent/AU668829B2/en not_active Ceased
- 1994-06-07 KR KR1019950700453A patent/KR100304072B1/ko not_active Expired - Fee Related
1995
- 1995-02-06 NO NO950432A patent/NO303449B1/no unknown
- 1995-02-07 FI FI950535A patent/FI112078B/fi active

Also Published As

Publication number	Publication date
CA2141029C (en)	2000-07-25
NO950432L (no)	1995-03-13
PL180870B1 (pl)	2001-04-30
NO950432D0 (no)	1995-02-06
RU2139870C1 (ru)	1999-10-20
DE69422374D1 (de)	2000-02-03
CN1110479A (zh)	1995-10-18
FI950535L (fi)	1995-02-07
BR9405423A (pt)	1999-05-25
DE69422374T2 (de)	2000-06-29
DK0654031T3 (da)	2000-06-13
GB9311709D0 (en)	1993-07-21
WO1994029301A1 (en)	1994-12-22
JP3110461B2 (ja)	2000-11-20
EP0654031A1 (de)	1995-05-24
HU219199B (en)	2001-03-28
CN1046720C (zh)	1999-11-24
PL307350A1 (en)	1995-05-15
CA2141029A1 (en)	1994-12-22
NO303449B1 (no)	1998-07-13
RU95108553A (ru)	1996-11-20
HK1008673A1 (en)	1999-05-14
KR100304072B1 (ko)	2001-11-22
AU6966794A (en)	1995-01-03
AU668829B2 (en)	1996-05-16
FI950535A0 (fi)	1995-02-07
HU9500364D0 (en)	1995-05-29
ES2139744T3 (es)	2000-02-16
FI112078B (fi)	2003-10-31
ATE188215T1 (de)	2000-01-15
US5763606A (en)	1998-06-09
NZ267379A (en)	1997-04-24
JPH08505643A (ja)	1996-06-18
HUT73630A (en)	1996-08-28
EP0654031B1 (de)	1999-12-29

Publication	Publication Date	Title
EP0515157B1 (de)	1997-09-03	Verfahren zur diastereoselektiven Synthese von Nukleosiden
HK1002431B (en)	1998-08-21	Processes for the diastereoselective synthesis of nucleosides
US6051709A (en)	2000-04-18	Process for the diastereoselective synthesis of nucleoside analogues
FI102279B (fi)	1998-11-13	Välituotteita nukleosidien diastereoselektiivisiin synteesimenetelmiin