CN101701026B - Catalytic cracking method for guanosine - Google Patents
Catalytic cracking method for guanosine Download PDFInfo
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- CN101701026B CN101701026B CN2009101544990A CN200910154499A CN101701026B CN 101701026 B CN101701026 B CN 101701026B CN 2009101544990 A CN2009101544990 A CN 2009101544990A CN 200910154499 A CN200910154499 A CN 200910154499A CN 101701026 B CN101701026 B CN 101701026B
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- guanosine
- ribofuranose
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- 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 title claims abstract description 96
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 title claims abstract description 48
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 229940029575 guanosine Drugs 0.000 title claims abstract description 48
- 238000000034 method Methods 0.000 title claims abstract description 26
- 238000004523 catalytic cracking Methods 0.000 title abstract description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 106
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 239000002904 solvent Substances 0.000 claims abstract description 15
- 239000013078 crystal Substances 0.000 claims abstract description 4
- 239000000706 filtrate Substances 0.000 claims abstract description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 58
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 23
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 238000001953 recrystallisation Methods 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000012065 filter cake Substances 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 8
- 150000008064 anhydrides Chemical class 0.000 claims description 8
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- HMFHBZSHGGEWLO-TXICZTDVSA-N beta-D-ribose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-TXICZTDVSA-N 0.000 claims description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 claims description 4
- MLFHJEHSLIIPHL-UHFFFAOYSA-N isoamyl acetate Chemical compound CC(C)CCOC(C)=O MLFHJEHSLIIPHL-UHFFFAOYSA-N 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- PGMYKACGEOXYJE-UHFFFAOYSA-N pentyl acetate Chemical compound CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 2
- HFZLSTDPRQSZCQ-UHFFFAOYSA-N 1-pyrrolidin-3-ylpyrrolidine Chemical compound C1CCCN1C1CNCC1 HFZLSTDPRQSZCQ-UHFFFAOYSA-N 0.000 claims description 2
- UHOPWFKONJYLCF-UHFFFAOYSA-N 2-(2-sulfanylethyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCS)C(=O)C2=C1 UHOPWFKONJYLCF-UHFFFAOYSA-N 0.000 claims description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- YEJCDKJIEMIWRQ-UHFFFAOYSA-N Linopirdine Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC=CC=C2C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 YEJCDKJIEMIWRQ-UHFFFAOYSA-N 0.000 claims description 2
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- 229940022663 acetate Drugs 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- 229940043232 butyl acetate Drugs 0.000 claims description 2
- 238000007233 catalytic pyrolysis Methods 0.000 claims description 2
- 230000006837 decompression Effects 0.000 claims description 2
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims description 2
- 229940117955 isoamyl acetate Drugs 0.000 claims description 2
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 claims description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 2
- 229940011051 isopropyl acetate Drugs 0.000 claims description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 2
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229940017219 methyl propionate Drugs 0.000 claims description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 2
- TWSRVQVEYJNFKQ-UHFFFAOYSA-N pentyl propanoate Chemical compound CCCCCOC(=O)CC TWSRVQVEYJNFKQ-UHFFFAOYSA-N 0.000 claims description 2
- 229940090181 propyl acetate Drugs 0.000 claims description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 2
- GILZZWCROUGLIS-UHFFFAOYSA-N n-(9-acetyl-6-oxo-3h-purin-2-yl)acetamide Chemical compound N1C(NC(=O)C)=NC(=O)C2=C1N(C(C)=O)C=N2 GILZZWCROUGLIS-UHFFFAOYSA-N 0.000 abstract description 26
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000000047 product Substances 0.000 abstract description 6
- 239000003054 catalyst Substances 0.000 abstract description 4
- 230000008901 benefit Effects 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- ULGWSQDVFZIBKN-FDYHWXHSSA-N [(2R,3R,4S,5S)-3,4,5-triacetyl-3,4,5-trihydroxyoxolan-2-yl]methyl acetate Chemical compound C(C)(=O)[C@]1(O)[C@](O)([C@](O)([C@H](O1)COC(C)=O)C(C)=O)C(C)=O ULGWSQDVFZIBKN-FDYHWXHSSA-N 0.000 abstract 3
- 239000012535 impurity Substances 0.000 abstract 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 48
- 238000002360 preparation method Methods 0.000 description 32
- 239000007787 solid Substances 0.000 description 30
- 239000000843 powder Substances 0.000 description 24
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 9
- -1 acyl ribose Chemical compound 0.000 description 9
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 9
- 239000003814 drug Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 229930010555 Inosine Natural products 0.000 description 4
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 229960003786 inosine Drugs 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 229960000329 ribavirin Drugs 0.000 description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000005336 cracking Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- QNXFUWFRTWSSOK-UHFFFAOYSA-N n-acetyl-n-(6-oxo-3,7-dihydropurin-2-yl)acetamide Chemical compound O=C1NC(N(C(C)=O)C(=O)C)=NC2=C1NC=N2 QNXFUWFRTWSSOK-UHFFFAOYSA-N 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- WYXSYVWAUAUWLD-SHUUEZRQSA-N 6-azauridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=N1 WYXSYVWAUAUWLD-SHUUEZRQSA-N 0.000 description 1
- 229940124321 AIDS medicine Drugs 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 description 1
- 229960001203 stavudine Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
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- Saccharide Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a catalytic cracking method for guanosine which is shown in the formula (I). The catalytic cracking method for guanosine comprises the following steps: the guanosine which is shown in the formula (I) and acetic anhydride react at 50-140 DEG C under the action of catalyst, and the reaction process is tracked; after the reaction finishes, the reaction solution is filtered to obtain filtrated cake A and filtrate A, and the filtrated cake A is washed and dried to obtain N2, 9-diacetylguanine showed in the formula (III); the filtrate A is postprocessed to obtain crude 1, 2, 3, 5-O-tetraacetyl-Beta-D-ribofuranose, and then the crude 1, 2, 3, 5-O-tetraacetyl-Beta-D-ribofuranose is recrystallized with recrystallizing solvent to obtain 1, 2, 3, 5-O-tetraacetyl-Beta-D-ribofuranose crystal. The catalytic cracking method for guanosine uses less catalyst which is cheap and easy to obtain, is convenient for operation, needs low temperature for reaction, ensures that the product has good color, excellent quality, high yield, less impurities and low production cost and is suitable for large-scale industrial production, thereby having obvious implementation value and social and economic benefits.
Description
(1) invention field
The present invention relates to a kind of catalytic material cracking preparation 1,2,3 that is with the guanosine, 5-O-is tetra-acetylated-β-D-ribofuranose or N
2, the method for 9-diacetylguanine.
(2) background technology
1,2,3,5-O-is tetra-acetylated-and β-D-ribofuranose (being called for short tetrem acyl ribose) is a kind of important medicine intermediate, can be used for synthetic broad-spectrum antiviral medicament ribavirin, novel antitumour drug 5 FU 5 fluorouracil, anti-AIDS drug stavudine etc.N
29-diacetylguanine (abbreviation diacetylguanine) is a kind of important nucleoside medicine midbody; To its direct alkylation or glycosylation is the important channel of medicines such as synthetic acyclovir, ganciclovir; And these medicines have good herpes, and the varicella virus effect is so the demand to diacetylguanine is bigger on the market.
Before the present invention made, Beranek etc. were at " Nucleic Acids Research " (1976,3 (5): the Acetylation and cleavage of perinea nucleon sides that is printed 1387-1392); Synthesisof 6-azauri-Dine; 5-fluroruridine, reported first is that raw material and aceticanhydride-Glacial acetic acid min. 99.5 reaction make tetrem acyl ribose with the inosine in and 5-methyluridine one literary composition, wherein Glacial acetic acid min. 99.5 plays katalysis; Make tetrem acyl ribose; Make with extra care with ETHYLE ACETATE, yield is 47%, and this method yield is low.(2001,18 (1): adopt tosic acid in the synthetic literary composition of the ribavirin of report 27) is catalyzer to Luo Xiaoyan etc., and catalysis inosine and aceticanhydride reaction obtain tetrem acyl ribose, and yield brings up to 84% in " fine chemistry industry ".The inosine price is more cheap, is easy to suitability for industrialized production, and this method is widely used, but is difficult to be fully used by the xanthoglobulin after the cracking of inosine acidylate, Gu cost is still higher.(1982,11:1-3) describing with Nucleotide in the technical study of the broad-spectrum antiviral drug-ribavirin of report is that raw material makes tetrem acyl ribose through guanosine and the acetic acid-Glacial acetic acid min. 99.5 reaction that hydrolysis makes, and yield is 51% at " medicine industry " in old these rivers etc.The shortcoming of this synthetic route is to be that raw material need pass through two-step reaction and just can obtain tetrem acyl ribose with Nucleotide, complex steps, and productive rate is low.Cai Wenyang is at " Chinese Journal of Pharmaceuticals " (1996; 27 (5): 232-235) 1,2,3 of middle report; It is raw material that the novel synthesis of 4-O-tetrem acyl-β-D-ribofuranose is told about with the adenosine; Zeo-karb is made catalyzer, and step cut-out, acetylize make tetrem acyl ribose, and yield is 84%.The resin price height that this route is used, recovery set is low with rate, and the price of VITAMIN B4 is also expensive than guanosine, and the production cost of this route is very high as a whole, is not suitable for industrialized production.
(3) summary of the invention
The technical problem that the present invention will solve be to provide a kind of easy and simple to handle, product color good, foreign matter content is few, production cost is low, reaction yield is high 1,2,3,5-O-is tetra-acetylated-β-D-ribofuranose or N
2, the chemical synthesis process of 9-diacetylguanine.
Technical scheme of the present invention is following:
A kind ofly preparing 1,2,3 shown in the formula (II) suc as formula the guanosine catalytic pyrolysis shown in (I), 5-O-is tetra-acetylated-N shown in β-D-ribofuranose or the formula (III)
2, the method for 9-diacetylguanine, described method is: suc as formula guanosine, the aceticanhydride shown in (I); Under the effect of catalyzer, reaction under 50～140 ℃ of temperature condition, TLC follows the tracks of reaction; After reaction finishes; Reacting liquid filtering, filter cake A and filtrating A, filter cake A washing, dry must be suc as formula the N shown in (III)
2, the 9-diacetylguanine; Filtrating A aftertreatment obtains 1,2,3, and 5-O-is tetra-acetylated-β-D-ribofuranose bullion, and is said 1,2,3, and 5-O-is tetra-acetylated-β-D-ribofuranose bullion gets 1,2,3 with the recrystallization solvent recrystallization, and 5-O-is tetra-acetylated-β-D-ribofuranose crystal; What the guanosine shown in the said formula (I), aceticanhydride amount of substance compared is 1: 5～50; The ratio of the amount of substance of the guanosine shown in the said formula (I), catalyzer is 1: 0.0001～0.1, and described catalyzer is the mixture of following one or more arbitrary proportions: trifluoroacetic anhydride, trifluoroacetic acid, trichoroacetic acid(TCA), trifluoromethanesulfonic acid or trifluoromethanesulfanhydride anhydride;
The inventive method can be used for separately preparation 1,2,3, and 5-O-is tetra-acetylated-N shown in β-D-ribofuranose or the formula (III)
2, the 9-diacetylguanine also can adopt the filter cake of reaction solution and filtrating to obtain this two compounds respectively respectively.
Filtrating A post-treating method of the present invention is: filtrating A underpressure distillation, and add water after the residuum cooling and stir, to filter, filter cake B washing, drying obtain 1,2,3, and 5-O-is tetra-acetylated-β-D-ribofuranose bullion.
The preferred ETHYLE ACETATE that uses of said filter cake A washing washs.Said filter cake B bath water washs.
Catalyzer of the present invention is the mixture of following one or more arbitrary proportions; Trifluoroacetic anhydride, trifluoroacetic acid, trichoroacetic acid(TCA), trifluoromethanesulfonic acid or trifluoromethanesulfanhydride anhydride are preferably the mixing of following one or more arbitrary proportions: trifluoroacetic acid or trifluoromethanesulfonic acid.
Recrystallization solvent of the present invention is the combination of following one or more arbitrary proportions: methyl acetate, ETHYLE ACETATE, propyl acetate, butylacetate, isopropyl acetate, isobutyl acetate, pentyl acetate, Isoamyl Acetate FCC, methyl propionate, ethyl propionate, propyl propionate, butyl propionate, amyl propionate, acetone, butanone, ether, propyl ether, isopropyl ether, butyl ether, THF, methyl alcohol, ethanol, propyl alcohol, Virahol or water; The combination of preferred following one or more arbitrary proportions: ETHYLE ACETATE, acetone, methyl alcohol, ethanol, propyl alcohol, Virahol or water most preferably are Virahol or water.
The ratio of the amount of substance of guanosine of the present invention, aceticanhydride is 1～5: 50, be preferably 1: 8～and 15.
The amount of substance value ratio of guanosine according to the invention, catalyzer is 1: 0.0001～0.01, be preferably 1: 0.001～and 0.01.
The quality consumption of described recrystallization solvent is 1,2,3,5-O-is tetra-acetylated-and 0.1～100 times of β-D-ribofuranose bullion quality, preferred 0.5～5 times.
Temperature of reaction of the present invention is 50～140 ℃, preferred 70～120 ℃.Reaction times is generally at 1～80 hour, preferred 4～45 hours.
The inventive method adopts trifluoroacetic acid, trichoroacetic acid(TCA), trifluoromethanesulfonic acid, trifluoroacetic anhydride or trifluoromethanesulfanhydride anhydride; As guanosine and aceticanhydride acidylate scission reaction catalyzer, the catalytic activity of catalyzer is high, and catalyst levels is few; All catalyzer all are soluble in recrystallization solvent; Easy to operate, the product color that obtains, quality all improve greatly, the N that makes
2, 9-diacetylguanine yield can reach more than 90%, and purity can reach 99.7%, gained 1; 2,3,5-O-is tetra-acetylated-and the yield of β-D-ribofuranose can reach more than 85%; Purity can reach 99.5%, and the purposes of these two kinds of products is bigger, and the cost of whole technological process is reduced.
In sum; Compared with prior art; It is few, cheap and easy to get that preparation method provided by the invention has a catalyst levels; Advantages such as easy and simple to handle, temperature of reaction is low, product color good, quality product is excellent, productive rate is high, foreign matter content is few, production cost is low, suitable large-scale industrial production have tangible implementary value and society, economic benefit.
(3) embodiment
Below in conjunction with embodiment the present invention is described further, but protection scope of the present invention is not limited to this.
Embodiment 1
Molar ratio is a guanosine: aceticanhydride: trifluoromethanesulfonic acid=1: 8: 0.001
In the there-necked flask that TM and churned mechanically 250mL are housed, add 42.5g guanosine, 122g aceticanhydride, the 0.023g trifluoromethanesulfonic acid; Open and stir, be heated to 140 ℃, insulation to reaction finishes (confirming reaction end by TLC); Reaction solution is cooled to 20 ℃; Filtration obtains filter cake and filtrating, and filter cake obtains off-white color pressed powder N with an amount of ETHYLE ACETATE washing after drying
2, 9-diacetylguanine 32.4g, yield 91.7% is (in guanosine, down together.), be 99.7% through detecting purity (the performance liquid chromatography area normalization method is called for short HPLC, down with.); Filtrate decompression is steamed and is removed acetic acid and aceticanhydride, obtains the syrupy shape material, and the cooling back adds 150mL water stirs, and has solid to separate out, and leaves standstill, and filters, and uses the less water washing leaching cake, and drying obtains tetrem acyl ribose bullion.Gained tetrem acyl ribose bullion adds the 50mL re-crystallizing in ethyl acetate, gets 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white crystal 39.63g, and yield 84.14% is 99.5% through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 2
Catalyzer changes trifluoromethanesulfanhydride anhydride into, and molar ratio is a guanosine: aceticanhydride: trifluoromethanesulfanhydride anhydride=1: 8: 0.001, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 32.3g, yield 91.4% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 40.5g, yield 86.0% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 3
Catalyzer changes trifluoroacetic acid into, and molar ratio is a guanosine: aceticanhydride: trifluoroacetic acid=1: 8: 0.001, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 31.4g, yield 89.09% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 39.5g, yield 83.9% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 4
Catalyzer changes trifluoroacetic anhydride into, and molar ratio is a guanosine: aceticanhydride: trifluoroacetic anhydride=1: 8: 0.001, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 32.78g, yield 92.91% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 39.0g, yield 82.8% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 5
Catalyzer changes trifluoromethanesulfonic acid and trifluoroacetic acid into, and molar ratio is a guanosine: aceticanhydride: trifluoromethanesulfonic acid: trifluoroacetic acid=1: 8: 0.001: 0.001, and other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 32.45g, yield 91.98% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 39.4g, yield 83.6% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 6
Catalyzer changes trichoroacetic acid(TCA) into, and molar ratio is a guanosine: aceticanhydride: trichoroacetic acid(TCA)=1: 8: 0.001, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 32.25g, yield 91.41% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 39.2g, yield 83.2% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 7
Catalyzer is a trifluoromethanesulfonic acid, and molar ratio is a guanosine: aceticanhydride: trifluoroacetic acid=1: 8: 0.005, temperature of reaction change 50 ℃ into, and other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 30.9g, yield 87.6% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 38.0g, yield 80.6% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 8
Catalyzer is a trifluoroacetic acid, and molar ratio changes guanosine into: aceticanhydride: trifluoroacetic acid=1: 8: 0.003, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 31.9g, yield 90.6% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 39.0g, yield 82.7% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 9
Catalyzer is a trifluoroacetic acid, and molar ratio changes guanosine into: aceticanhydride: trifluoroacetic acid=1: 5: 0.003, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 31.1g, yield 88.2% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 38.4g, yield 81.5% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 10
Catalyzer is a trifluoroacetic acid, and molar ratio is a guanosine: aceticanhydride: trifluoroacetic acid=1: 10: 0.008, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 32.7g, yield 92.6% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 39.3g, yield 83.5% is 99.5% (HPLC) through detecting purity, fusing point is 80 ℃～83 ℃.
Embodiment 11
Catalyzer is a trifluoromethanesulfonic acid, and molar ratio is a guanosine: aceticanhydride: trifluoromethanesulfonic acid=1: 10: 0.01, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 33.1g, yield 93.7% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 40.1g, yield 85.2% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 12
Catalyzer is a trifluoroacetic anhydride, and molar ratio changes guanosine into: aceticanhydride: trifluoroacetic anhydride=1: 10: 0.01, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 33.1g, yield 93.8% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 40.2g, yield 85.5% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 13
Catalyzer is a trifluoromethanesulfonic acid, and molar ratio is a guanosine: aceticanhydride: trifluoromethanesulfonic acid=1: 20: 0.01, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 32.9g, yield 93.5% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 40.0g, yield 84.9% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 14
Catalyzer is a trifluoroacetic acid, and molar ratio is a guanosine: aceticanhydride: trifluoroacetic acid=1: 50: 0.01, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 33.2g, yield 94.2% is 99.7% through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 40.4g, yield 85.8% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 15
Catalyzer is a trifluoroacetic acid, and molar ratio changes guanosine into: aceticanhydride: trifluoroacetic acid=1: 10: 0.0001, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 31.8g, yield 90.1% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 39.4g, yield 83.6% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 16
Catalyzer is a trifluoroacetic acid, and molar ratio changes guanosine into: aceticanhydride: trifluoroacetic acid=1: 50: 0.1, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 31.3g, yield 88.7% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 39.2g, yield 83.2% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 17
Catalyzer is a trifluoromethanesulfonic acid, and molar ratio is a guanosine: aceticanhydride: trifluoromethanesulfonic acid=1: 30: 0.008, other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 33.4g, yield 94.8% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 40.6g, yield 86.1% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 18
Catalyzer is trifluoromethanesulfonic acid and trifluoroacetic acid, and molar ratio is a guanosine: aceticanhydride: trifluoromethanesulfonic acid: trifluoroacetic acid=1: 12: 0.005: 0.005, and other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 33.9g, yield 96.0% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 38.9g, yield 82.7% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 19
Catalyzer is a trifluoromethanesulfonic acid, and molar ratio is a guanosine: aceticanhydride: trifluoromethanesulfonic acid=1: 12: 0.001, temperature of reaction are 70 ℃, and other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 31.5g, yield 89.1% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 38.2g, yield 81.2% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 20
Catalyzer is a trifluoroacetic acid, and molar ratio is a guanosine: aceticanhydride: trifluoroacetic acid=1: 15: 0.001, temperature of reaction are 70 ℃, and other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 32.0g, yield 90.7% is 99.7% (HPLC) through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 38.6g, yield 81.9% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 21
Catalyzer is a trifluoromethanesulfanhydride anhydride, and molar ratio is a guanosine: aceticanhydride: trifluoromethanesulfanhydride anhydride=1: 15: 0.01, temperature of reaction are 70 ℃, and other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 32.0g, yield 90.7% is 99.7% through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 38.4g, yield 81.6% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 22
Catalyzer is a trifluoroacetic acid, and molar ratio is a guanosine: aceticanhydride: trifluoroacetic acid=1: 15: 0.001, temperature of reaction are 120 ℃, and other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 32.5g, yield 92.2% is 98.9% through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 38.6g, yield 82.0% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 23
Catalyzer is a trifluoroacetic anhydride, and molar ratio is a guanosine: aceticanhydride: trifluoroacetic anhydride=1: 15: 0.01, temperature of reaction are 120 ℃, and other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 33.1g, yield 93.9% is 98.9% through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 37.9g, yield 80.5% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 24
Catalyzer is a trifluoromethanesulfonic acid, and molar ratio is a guanosine: aceticanhydride: trifluoromethanesulfonic acid=1: 8: 0.01, temperature of reaction are 120 ℃, and other condition preparation process is all with embodiment 1.Get N
2, 9-diacetylguanine white powder 33.8g, yield 95.7% is 98.9% through detecting purity; Get 1,2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 38.1g, yield 80.8% is 99.5% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 25
1,2,3,4-O-tetrem acyl-β-D-ribofuranose bullion recrystallization solvent changes water into; Other condition preparation process gets 1,2,3 all with embodiment 1; 4-O-tetrem acyl-β-D-ribofuranose white solid 40.5g, yield 86.0% is 98.9% (HPLC) through detecting purity, fusing point is 82 ℃～83 ℃.
Embodiment 26
1,2,3; 4-O-tetrem acyl-β-D-ribofuranose bullion recrystallization solvent changes Virahol into, and other condition preparation process gets 1 all with embodiment 1; 2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 41.20g; Yield 87.47% is 99.5% (HPLC) through detecting purity, and fusing point is 82 ℃～83 ℃.
Embodiment 27
1,2,3; 4-O-tetrem acyl-β-D-ribofuranose bullion recrystallization solvent changes methyl alcohol into, and other condition preparation process gets 1 all with embodiment 1; 2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 39.8g; Yield 84.6% is 99.5% (HPLC) through detecting purity, and fusing point is 82 ℃～83 ℃.
Embodiment 28
1,2,3; 4-O-tetrem acyl-β-D-ribofuranose bullion recrystallization solvent changes ethanol into: (v/v=1: 1), other condition preparation process gets 1 all with embodiment 1 to water; 2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 39.9g; Yield 84.8% is 99.5% (HPLC) through detecting purity, and fusing point is 82 ℃～83 ℃.
Embodiment 29
1,2,3; 4-O-tetrem acyl-β-D-ribofuranose bullion recrystallization solvent changes methyl alcohol into: (v/v=1: 1), other condition preparation process gets 1 all with embodiment 1 to water; 2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 40.3g; Yield 85.6% is 99.5% (HPLC) through detecting purity, and fusing point is 82 ℃～83 ℃.
Embodiment 30
1,2,3; 4-O-tetrem acyl-β-D-ribofuranose bullion recrystallization solvent changes ethanol into: (v/v=3: 1), other condition preparation process gets 1 all with embodiment 1 to water; 2,3,4-O-tetrem acyl-β-D-ribofuranose white solid 40.3g; Yield 85.6% is 99.5% (HPLC) through detecting purity, and fusing point is 82 ℃～83 ℃.
Claims (10)
1. the guanosine catalytic pyrolysis shown in formula I prepares 1,2,3 shown in the formula II, and 5-O-is tetra-acetylated-N shown in β-D-ribofuranose or the formula III
2, the method for 9-diacetylguanine is characterized in that described method is: the guanosine shown in formula I, aceticanhydride; Under the effect of catalyzer, reaction under 50～140 ℃ of temperature condition, TLC follows the tracks of reaction; After reaction finishes; Reacting liquid filtering, filter cake A and filtrating A, filter cake A washing, dry N that must be shown in formula III
2, the 9-diacetylguanine; Filtrating A aftertreatment obtains 1,2,3, and 5-O-is tetra-acetylated-β-D-ribofuranose bullion, and is said 1,2,3, and 5-O-is tetra-acetylated-β-D-ribofuranose bullion gets 1,2,3 with the recrystallization solvent recrystallization, and 5-O-is tetra-acetylated-β-D-ribofuranose crystal; The ratio of the guanosine shown in the said formula I, aceticanhydride amount of substance is 1: 5～50; The ratio of the amount of substance of the guanosine shown in the said formula I, catalyzer is 1: 0.0001～0.1, and described catalyzer is the mixture of following one or more arbitrary proportions: trifluoroacetic anhydride, trifluoroacetic acid, trichoroacetic acid(TCA), trifluoromethanesulfonic acid or trifluoromethanesulfanhydride anhydride;
2. the method for claim 1 is characterized in that described filtrating A post-treating method is: the filtrate decompression distillation, and add water after the residuum cooling and stir, to filter, filter cake B washing, drying obtain 1,2,3, and 5-O-is tetra-acetylated-β-D-ribofuranose bullion.
3. the method for claim 1 is characterized in that described recrystallization solvent is the mixing of following one or more arbitrary proportions: methyl acetate, ETHYLE ACETATE, propyl acetate, butylacetate, isopropyl acetate, isobutyl acetate, pentyl acetate, Isoamyl Acetate FCC, methyl propionate, ethyl propionate, propyl propionate, butyl propionate, amyl propionate, acetone, butanone, ether, propyl ether, isopropyl ether, butyl ether, THF, methyl alcohol, ethanol, propyl alcohol, Virahol or water.
4. the method for claim 1 is characterized in that described recrystallization solvent quality consumption is 1,2,3,5-O-is tetra-acetylated-and 0.1～100 times of β-D-ribofuranose bullion quality.
5. the method for claim 1 is characterized in that described catalyzer is following one or both mixing with arbitrary proportion: trifluoroacetic acid or trifluoromethanesulfonic acid.
6. method as claimed in claim 3 is characterized in that described recrystallization solvent is the mixing of following one or more arbitrary proportions: ETHYLE ACETATE, acetone, methyl alcohol, ethanol, propyl alcohol, Virahol or water.
7. the method for claim 1, the ratio that it is characterized in that the amount of substance of the guanosine shown in the said formula I, aceticanhydride is 1: 8～15.
8. the method for claim 1, the ratio that it is characterized in that the amount of substance of the guanosine shown in the said formula I, catalyzer is 1: 0.001～0.01.
9. the method for claim 1 is characterized in that temperature of reaction is 70～120 ℃.
10. the method for claim 1 is characterized in that described filter cake A washing washs with ETHYLE ACETATE.
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| CN104910215B (en) * | 2015-05-22 | 2018-02-13 | 浙江工业大学 | A kind of method that raffinate is crystallized using 1,2,3,5-Tetra-O-Acetyl-D-Ribose after nucleolytic |
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| CN111440170B (en) * | 2020-04-22 | 2021-09-14 | 通辽德胜生物科技有限公司 | Method for synthesizing guanine by using guanosine |
| CN111440171A (en) * | 2020-04-23 | 2020-07-24 | 洛阳德胜生物科技股份有限公司 | Method for synthesizing guanine by hydrolysis of guanosine |
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| 罗晓燕等.三氮唑核苷的合成.《精细化工》.2001,第18卷(第1期),27－28. * |
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Address after: City Zhejiang University of Technology Hangzhou Zhaohui six districts of 310014 cities in Zhejiang Province under the Patentee after: Zhejiang University of Technology Patentee after: ZHEJIANG CHENG YI PHARMACEUTICAL CO., LTD. Address before: City Zhejiang University of Technology Hangzhou Zhaohui six districts of 310014 cities in Zhejiang Province under the Patentee before: Zhejiang University of Technology Patentee before: Zhejiang Chengyi Pharmaceutical Industry Co., Ltd. |