合成路线:The treatment of 2,3-O-dimesyl-5-O-(4-methoxybenzyl)-1-O-methyl-alpha-D-xylofuranose (XXX) with NaBH4 gives 3-deoxy-5-O-(4-methoxybenzyl)-1-O-methyl-alpha-D-xylofuranose (XXXI),which is fluorinated with diethylamido sulfur trifluoride as before,yielding 2,3-dideoxy-2-fluoro-5-O-(4-methoxybenzyl)-alpha-D-arabinofuranose (XXXII).The condensation of (XXXII) with adenine (XXXIII) by means of acetyl bromide affords 9-[2,3-dideoxy-2-fluoro-5-O-(4-methoxybenzyl)-beta-D-arabinofuraosyl]adenine (XXXIV),which is finally deprotected by hydrogenation over Pd/C in ethanol.
参考文献标题:alpha-D-Pentofuranoside derivs.,process for preparing the same and their use
文献作者:Stadelmann,B.
参考来源:WO 9606103
合成路线:The selective silylation of 2-deoxy-2-fluoro-1-O-methyl-beta-D-arabinofuranose (XIII) with tert-butyldiphenylsilyl chloride (TBDPS-Cl) and imidazole in DMF gives the 5-O-silylated sugar (XXIV),which is treated with CS2/NaH/methyl iodide in DMF to yield compound (XXV).The reduction of (XXV) with tributyltin hydride and AIBN in refluxing toluene affords 2,3-dideoxy-2-fluoro-5-O-(tert-butyldiphenylsilyl)-beta-D-arabinofuranose (XXVI),which is treated with HBr in acetic acid to yield the bromosugar (XXVII).The condensation of (XXVII) with 6-chloropurine (V) in hot acetonitrile gives 6-chloro-9-[2,3-dideoxy-2-fluoro-5-O-(tert-butyldiphenylsilyl)-beta-D-arabinofuranosyl]purine (XXVIII),which is desilylated with tetrabutylammonium fluoride in THF,yielding 6-chloro-9-[2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl]purine (XXIX).Finally,this compound is treated with methanolic ammonia at 105 C as before.
参考文献标题: 2'-Fluorofuranosyl derivs.and methods for preparing 2'-fluoropyrimidine and 2'-fluoropurine nucleosides
文献作者:Marquez,V.E.; Siddiqui,M.A.; Driscoll,J.S.; Wysocki,R.J.Jr.(US Department of Health & Human Services)
参考来源:US 5817799
合成路线:The TLC monitored reaction of 1,3-di-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranose (III) with 30% HBr in acetic acid gives the bromosugar (IV),which is condensed with 6-chloropurine (V) in refluxing dichloromethane,yielding the chloropurine derivative (VI).The reaction of (VI) with methanolic NH3 at 100 C in a steel bomb affords 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (VII),which is selectively silylated with tert-butyldimethylsilyl chloride (TBDMS-Cl) and imidazole in DMF,giving the 5'-O-silyl derivative (VIII).The reaction of (VIII) with phenyl chlorothioformate by means of dimethylaminopyridine in DMF yields the thiocarbonate (IX),which is reduced with tributyltin hydride and AIBN in hot toluene,affording 9-[2,3-dideoxy-2-fluoro-5-O-(tert-butyldimethylsilyl)-beta-D-arabinofuranosyl]adenine (X).Finally,this compound is desilylated with tetrabutylammonium fluoride in THF.
参考文献标题:Acid-stable 2'-fluoro purine dideoxynucleosides as active agents against HIV
文献作者:Marquez,V.E.; Tseng,C.K.-H.; Mitsuya,H.; Aoki,S.; Kelley,J.A.; Ford,H.Jr.; Roth,J.S.; Broder,S.; Johns,D.G.; Driscoll,J.S.
参考来源:J Med Chem 1990,33(3),978-85
合成路线:The selective tritylation of cordycepin (3'-deoxyadenosine) (I) with trityl chloride in pyridine gives the 5'-O-trityl derivative (II),which is then fluorinated with diethylamido sulfur trifluoride in refluxing dichloromethane and deprotected with hot 80% acetic acid.
合成路线:The TLC monitored reaction of 1,3-di-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranose (III) with 30% HBr in acetic acid gives the bromosugar (IV),which is condensed with 6-chloropurine (V) in refluxing dichloromethane,yielding the chloropurine derivative (VI).The reaction of (VI) with methanolic NH3 at 100 C in a steel bomb affords 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (VII),which is selectively silylated with tert-butyldimethylsilyl chloride (TBDMS-Cl) and imidazole in DMF,giving the 5'-O-silyl derivative (VIII).The reaction of (VIII) with phenyl chlorothioformate by means of dimethylaminopyridine in DMF yields the thiocarbonate (IX),which is reduced with tributyltin hydride and AIBN in hot toluene,affording 9-[2,3-dideoxy-2-fluoro-5-O-(tert-butyldimethylsilyl)-beta-D-arabinofuranosyl]adenine (X).Finally,this compound is desilylated with tetrabutylammonium fluoride in THF.
合成路线:The reaction of 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranose (XI) with HBr in acetic acid gives the bromosugar (XII),which is methylated with methanol/K2CO3 in THF,yielding the 1-O-methyl glucoside (XIII).The selective benzoylation of (XIII) with benzoyl chloride in pyridine at -30 C affords the 5-O-benzoyl glucoside (XIV),which is treated with CS2/methyl iodide and NaH in DMF,giving compound (XV).The reduction of (XV) with tributyltin hydride and AIBN in refluxing toluene yields the 3-deoxy glucoside (XVI),which is condensed with 6-chloropurine (V) in refluxing hexamethyldisylazane,affording 9-(5-O-benzoyl-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (XVII).Finally,this compound is debenzoylated with methanolic ammonia at 100 C in a sealed tube.
合成路线:The regioseletive deacetylation of 9-(2,5-diacetoxy-3-bromo-3-deoxy-beta-D-xylofuranosyl)adenine (XVIII) by means of beta-cyclodextrin/NaHCO3 in water or hydrazine monohydrate in ethanol gives 9-(5-acetoxy-3-bromo-3-deoxy-beta-D-xylofuranosyl)adenine (XIX),which is debrominated by hydrogenation over Pd/C in acetonitrile/water,affording 9-(5-acetoxy-3-deoxy-beta-D-xylofuranosyl)adenine (XX).Finally,this compound is fluorinated by means of diethylamido sulfur trifluoride in refluxing dichloromethane,yielding (XXI) and deacetylated with NH3 to the target compound.
合成路线:The controlled reaction of 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranose (XI) with HBr in acetic acid gives the bromosugar (XXII),which is condensed with 6-chloropurine (V) as before,yielding 6-chloro-9-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-beta-D-arabinofuranosyl)purine (XXIII).Finally,this compound is treated with ammonia in methanol as before to afford intermediate 9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (VII).
合成路线:The selective silylation of 2-deoxy-2-fluoro-1-O-methyl-beta-D-arabinofuranose (XIII) with tert-butyldiphenylsilyl chloride (TBDPS-Cl) and imidazole in DMF gives the 5-O-silylated sugar (XXIV),which is treated with CS2/NaH/methyl iodide in DMF to yield compound (XXV).The reduction of (XXV) with tributyltin hydride and AIBN in refluxing toluene affords 2,3-dideoxy-2-fluoro-5-O-(tert-butyldiphenylsilyl)-beta-D-arabinofuranose (XXVI),which is treated with HBr in acetic acid to yield the bromosugar (XXVII).The condensation of (XXVII) with 6-chloropurine (V) in hot acetonitrile gives 6-chloro-9-[2,3-dideoxy-2-fluoro-5-O-(tert-butyldiphenylsilyl)-beta-D-arabinofuranosyl]purine (XXVIII),which is desilylated with tetrabutylammonium fluoride in THF,yielding 6-chloro-9-[2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl]purine (XXIX).Finally,this compound is treated with methanolic ammonia at 105 C as before.
合成路线:The treatment of 2,3-O-dimesyl-5-O-(4-methoxybenzyl)-1-O-methyl-alpha-D-xylofuranose (XXX) with NaBH4 gives 3-deoxy-5-O-(4-methoxybenzyl)-1-O-methyl-alpha-D-xylofuranose (XXXI),which is fluorinated with diethylamido sulfur trifluoride as before,yielding 2,3-dideoxy-2-fluoro-5-O-(4-methoxybenzyl)-alpha-D-arabinofuranose (XXXII).The condensation of (XXXII) with adenine (XXXIII) by means of acetyl bromide affords 9-[2,3-dideoxy-2-fluoro-5-O-(4-methoxybenzyl)-beta-D-arabinofuraosyl]adenine (XXXIV),which is finally deprotected by hydrogenation over Pd/C in ethanol.
合成路线:The reaction of 2,3-O-isopropylidene-D-ribofuranose (XXXV) with 4-methylbenzoyl chloride (XXXVI) by means of pyridine in butyl acetate gives 2,3-O-isopropylidene-5-O-(4-methylbenzoyl)-D-ribofuranose (XXXVII),which is methylated by means of NaH and dimethylsulfate in THF to yield the expected methyl ribofuranoside (XXXVIII).The hydrolysis of the acetonide group of (XXXVIII) with trifluoromethanesulfonic acid in acetonitrile affords 1-O-methyl-5-O-(4-methylbenzoyl)-alpha-D-ribofuranose (XXXIX),which is treated with SO2Cl2/triethylamine in butyl acetate to give the cyclic sulfate (XL).The reduction of (XL) with NaBH4 in THF yields 3-deoxy-1-O-methyl-5-O-(4-methylbenzoyl)-alpha-D-ribofuranose (XLI),which is treated with trifluoromethanesulfonic anhydride and tetrabutylammonium fluoride in dichloromethane/pyridine to afford 2,3-dideoxy-2-fluoro-1-O-methyl-alpha-D-arabinofuranose (XLII).The reaction of (XLII) with HBr in acetic acid as before gives the bromosugar (XLIII),which is condensed with 6-chloro-9-(trimethylsilyl)purine (XLIV) in dichloromethane to yield 6-chloro-9-[2,3-dideoxy-2-fluoro-5-O-(4-methylbenzoyl)-beta-D-arabinofuranosyl]purine (XLV).Finally,this compound is treated with ammonia in methanol at 90 C.
参考文献标题:Lodenosine
文献作者:Castar,J.; Graul,A.; Silvestre,J.S.
参考来源:Drugs Fut 1998,23(11),1176-1189
合成路线:The selective tritylation of cordycepin (3'-deoxyadenosine) (I) with trityl chloride in pyridine gives the 5'-O-trityl derivative (II),which is then fluorinated with diethylamido sulfur trifluoride in refluxing dichloromethane and deprotected with hot 80% acetic acid.
参考文献标题:Synthesis and anti-HIV activity of various 2'- and 3'-substituted 2',3'-dideoxyadenosines: A structure-activity analysis
文献作者:Herdewijn,P.; Pauwels,R.; Baba,M.; Balzarini,J.; De Clercq,E.
参考来源:J Med Chem 1987,30(11),2131-7
合成路线:The reaction of 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranose (XI) with HBr in acetic acid gives the bromosugar (XII),which is methylated with methanol/K2CO3 in THF,yielding the 1-O-methyl glucoside (XIII).The selective benzoylation of (XIII) with benzoyl chloride in pyridine at -30 C affords the 5-O-benzoyl glucoside (XIV),which is treated with CS2/methyl iodide and NaH in DMF,giving compound (XV).The reduction of (XV) with tributyltin hydride and AIBN in refluxing toluene yields the 3-deoxy glucoside (XVI),which is condensed with 6-chloropurine (V) in refluxing hexamethyldisylazane,affording 9-(5-O-benzoyl-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)adenine (XVII).Finally,this compound is debenzoylated with methanolic ammonia at 100 C in a sealed tube.
参考文献标题:2',3'-Dideoxy-2'-fluoro-ara-A,an acid-stable purine nucleoside active against human immunodeficiency virus (HIV)
文献作者:Marquez,V.E.; Tseng,C.K.-H.; Kelley,J.A.; Mitsuya,H.; Roth,J.S.; Broder,S.; Driscoll,J.S.
参考来源:Biochem Pharmacol 1987,36(17),2719-22
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