合成路线:The selective protection of 1,2-O-isopropylidene-D-xylofuranose (I) with Tbdms-Cl and pyridine gives the silyl ether (II),which is oxidized with CrO3,pyridine and Ac2O in dichloromethane to yield the ketone (III).Stereoselective addition of trimethylsilylacetylene (IV) to the ketone (III) by means of BuLi in THF affords the beta-adduct (V),which is desilylated by means of TBAF in THF to provide 3-C-ethynyl-2,3-o-isopropylidene-alpha-D-ribofuranose (VI).The selective monobenzoylation of (VI) with benzoyl chloride and pyridine gives the monobenzoate (VII),which is treated with HCl in methanol to cleave the isopropylidene protecting group and yield (VIII).The exhaustive benzoylation of (VIII) with benzoyl chloride and DMAP in pyridine at 100 C affords the tribenzoate (IX),which is treated with H2SO4 and Ac2O to provide the monoacetate (X).The condensation of (X) with cytosine (XI) by means of SnCl4 in acetonitrile gives the cytidine derivative (XII),which is finally debenzoylated by means of NH3 in methanol to yield the target ethynyl-cytidine derivative.
参考文献标题:Nucleosides and nucleotides.158.1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine,1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil,and their nucleobase analogues as new potential multifunctional antitumor nucleosides with a broad spectrum of activity
文献作者:Hattori,H.; Tanaka,M.; Fukushima,M.; Sasaki,T.; Matsuda,A.
参考来源:J Med Chem 1996,39(25),5005
合成路线:The selective protection of 1,2-O-isopropylidene-D-xylofuranose (I) with Tbdms-Cl and pyridine gives the silyl ether (II),which is oxidized with CrO3,pyridine and Ac2O in dichloromethane to yield the ketone (III).Stereoselective addition of trimethylsilylacetylene (IV) to the ketone (III) by means of BuLi in THF affords the beta-adduct (V),which is desilylated by means of TBAF in THF to provide 3-C-ethynyl-2,3-o-isopropylidene-alpha-D-ribofuranose (VI).The selective monobenzoylation of (VI) with benzoyl chloride and pyridine gives the monobenzoate (VII),which is treated with HCl in methanol to cleave the isopropylidene protecting group and yield (VIII).The exhaustive benzoylation of (VIII) with benzoyl chloride and DMAP in pyridine at 100 C affords the tribenzoate (IX),which is treated with H2SO4 and Ac2O to provide the monoacetate (X).The condensation of (X) with cytosine (XI) by means of SnCl4 in acetonitrile gives the cytidine derivative (XII),which is finally debenzoylated by means of NH3 in methanol to yield the target ethynyl-cytidine derivative.
合成路线:The reaction of 1,2-O-isopropylidene-D-xylofuranose (I) with 4-chlorobenzoyl chloride (II) and TEA gives the 5-O-(4-chlorobenzoate) (III),which is oxidized with TEMPO and NaClO to yield the 3-oxo derivative (IV).The ethynylation of (IV) by means of trimethylsilylethynyl magnesium bromide (V) affords the 3-C-trimethylsilylethynyl derivative (VI),which is hydrolyzed by means of refluxing aqueous HCOOH to provide the 3-C-ethynylated sugar (VII).The acylation of (VII) by means of 4-chlorobenzoyl chloride (II),TEA and DMAP gives the tetrabenzoate sugar (VIII),which is used for the glycosylation of bis trimethylsilyl cytosine (IX) by means of SnCl4 to yield the protected precursor (X).Finally,this compound is desilylated and debenzoylated by means of DBU in hot methanol to afford the target nucleoside.
参考文献标题:Nucleosides and nucleotides.Part 212: Practical large-scale synthesis of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd),a potent antitumor nucleoside.Isobutyryloxy group as an efficient anomeric leaving group in the Vorbruggen glycosylation
文献作者:Nomura,M.; Sato,T.; Masato,W.; Tanaka,M.; Asao,T.; Shuto,S.; Matsuda,A.
参考来源:Tetrahedron 2002,58(7),1279
合成路线:The selective protection of 1,2-O-isopropylidene-D-xylofuranose (I) with Tbdms-Cl and pyridine gives the silyl ether (II),which is oxidized with CrO3,pyridine and Ac2O in dichloromethane to yield the ketone (III).Stereoselective addition of trimethylsilylacetylene (IV) to the ketone (III) by means of BuLi in THF affords the beta-adduct (V),which is desilylated by means of TBAF in THF to provide 3-C-ethynyl-2,3-o-isopropylidene-alpha-D-ribofuranose (VI).The selective monobenzoylation of (VI) with benzoyl chloride and pyridine gives the monobenzoate (VII),which is treated with HCl in methanol to cleave the isopropylidene protecting group and yield (VIII).The exhaustive benzoylation of (VIII) with benzoyl chloride and DMAP in pyridine at 100 C affords the tribenzoate (IX),which is treated with H2SO4 and Ac2O to provide the monoacetate (X).The condensation of (X) with cytosine (XI) by means of SnCl4 in acetonitrile gives the cytidine derivative (XII),which is finally debenzoylated by means of NH3 in methanol to yield the target ethynyl-cytidine derivative.
参考文献标题:Synthesis and antitumor activity of 1-(3-C-ethynyl-beta-D-ribo-pentfuranosyl)cytosine,-uracil and their sugar modified derivatives
文献作者:Nozawa,E.; Hattori,H.; Shuto,S.; Tanaka,M.; Sasaki,T.; Matsuda,A.
参考来源:Nucleic Acids Symp Ser 1996,(35),31
合成路线:The reaction of cytidine (I) with benzoyl anhydride in dioxane gives N-benzoylcytidine (II),which is selectively monoprotected at the primary OH group by means of 4-methoxytrityl chloride and pyridine to yield N-benzoyl-5'O-(monomethoxytrityl)cytidine (III).The monosilylation of (III) by means of Tbdms-Cl and AgNO3 in pyridine/THF affords a mixture of the 3'-O-silyl (IV) and the desired 2'-O-silyl (V) derivative which is easily separated by flash chromatography.(The yield of the desired 2'-O-silyl isomer (V) can be improved by isomerization of the 3'-O-silyl isomer (IV) by means of pyridine in methanol at 70 C).The oxidation of (V) by means of CrO3 and Ac2O provides the 3'-oxonucleoside (VI),which is selectively deprotected by means of TsOH in chloroform/methanol to give compound (VII).The reaction of (VII) with trimethylsilylacetylene (VIII) by means of BuLi and CeCl3 in THF yields the protected ethynyl nucleoside (IX),which is debenzoylated by means of NH3 in methanol to afford the silylated nucleoside (X).Finally,this compound is treated with TBAF in THF to obtain the target ethynyl cytidine.
参考文献标题:A new laboratory scale synthesis for the anticancer drug 3'-C.ethynylcytidine
文献作者:Ludwig,P.S.; Schwender,R.A.; Schott,H.
参考来源:Synthesis (Stuttgart) 2002,(16),2387
产品链接: CAS No. 180300-43-0››