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Acycloguanosine, Aciclovir, Acyclovir, W-248-U, BW-248-U, Maynar, Viropump(former Brand Name), Genvir, Zovirax

阿昔洛韦Chemical Name: 9-(2-Hydroxyethoxymethyl)guanine; 2-Amino-6-hydroxy-9-(2-hydroxyethoxymethyl)purine; 2-Amino-9-[(2-hydroxyethoxy)methyl]-1,9-dihydro-6H-purin-6-one
CAS No. 59277-89-3
项目整合开发状态: Launched-1981
项目研究机构: GlaxoSmithKline (Originator), Biovail (Licensee), Ferrer (Licensee), Flamel (Formulation), SkyePharma (Formulation), Shionogi (Codevelopment)
合成路线:An efficient and selective process for the synthesis of acyclovir has been published:The reaction of guanine (I) with refluxing hexamethyldisilazane (HMDS) (II) by means of trifluoromethanesulfonic acid,elimination of the HMDS in excess and condensation of the resulting product with refluxing 1,3-dioxolane (III) gives 9-[2-(trimethylsilyloxy)ethoxymethyl]guanine (IV),which is finally hydrolyzed with refluxing acetic acid/water.
📌 参考资料/链接:
参考文献标题:Preparation of acyclovir
文献作者:Han,Y.-K.; Harrington,P.J.; Schloemer,G.C.(F.Hoffmann-La Roche AG)
参考来源:EP 0709385; JP 1996053451

📄 详细内容


合成路线:The reaction of benzonitrile (I) with refluxing ethylene glycol (II) gives ethylene glycol monobenzoate (III),which is chloromethylated with formaldehyde and dry HCl in CH2Cl2 affording 1-benzoyloxy-2-chloromethoxyethane (IV).The condensation of (IV) with 2,6-dichloropurine (V) by means of triethylamine in DMF yields 2,6-dichloro-9-(2-benzoyloxyethoxymethyl)purine (VI),which is aminated and debenzoylated by treatment with NH3 in methanol at 95 C in a pressure vessel giving 2-chloro-9-(2-hydroxyethoxymethyl)adenine (VII).The Sandmeyer reaction of (VII) with NaNO2 in acetic acid affords 2-chloro-9-(2-hydroxyethoxymethyl)hypoxanthine (VIII),which is finally amonolyzed with ammonia in methanol at 125 C in a pressure vessel.

合成路线:The condensation of guanine (IX) with refluxing hexamethyldisilazane followed by reaction with 1-benzoyloxy-2-chloromethoxyethane (IV) by means of triethylamine in refluxing benzene gives 9-(2-benzoyloxyethoxymethyl)guanine (X),which is finally hydrolyzed with ammonia in methanol at 80 C in a pressure vessel.

合成路线:The condensation of 2-amino 6 chloropurine (I) with 2-benzyioxyethoxymethyl chloride (II),by means of K2CO3 in DMF gives 2-amino-6 chloro 9-(2 benzyloxyethoxymethyl)purine (III),which is then dechlorinated by reduction with H2 over Pd/C in ethanol containing triethylamine.

参考文献标题:Purine derivs.
文献作者:Schaeffer,H.J.(Glaxo Wellcome plc)
参考来源:US 4294831


合成路线:The acetylation of guanine (I) or guanosine (II) with acetic anhydride gives the diacetyl guanine (III),which is condensed with 1,4-diacetoxy-2-oxabutane (IV) by means of TsOH to yield N,O-diacetyl acyclovir (V).Finally,this compound is deacetylated with NH3,NaOH or pyrrolidine at room temperature,or also with refluxing glycol.

合成路线:The reaction of 1,3-dichloro-2-propanol (I) with Bn-ONa gives 1,3-dibenzyloxy-2-propanol (II),which by reaction with paraformaldehyde and HCl is converted into the chloromethyl ether (III).The reaction of (III) with potassium acetate affords the acetoxymethyl ether (IV),which is condensed with diacetylguanine (V) by means of TsOH to provide fully protected ganciclovir (VI).Finally,this compound is debenzylated to (VII) with Pd(OH)2/cyclohexene and deacetylated with ammonia in methanol.

合成路线:The reaction of 4-(chloromethyl)-1,3-dioxolane (I) with Ac2O,HOAc and ZnCl2 gives the diacetoxy compound (II),which is treated with KOAc to yield the triacetoxy compound (III).The condensation of (III) with diacetyl guanine (IV) by means of ethylsulfonic acid affords the triacetyl ganciclovir (V),which is finally deacetylated with methylamine in methanol.

参考文献标题:Synthesis of acyclovir,ganciclovir and their prodrugs: A review
文献作者:Gao,H.; Mitra,A.K.
参考来源:Synthesis 2000,(3),329


合成路线:The reaction of benzonitrile (I) with refluxing ethylene glycol (II) gives ethylene glycol monobenzoate (III),which is chloromethylated with formaldehyde and dry HCl in CH2Cl2 affording 1-benzoyloxy-2-chloromethoxyethane (IV).The condensation of (IV) with 2,6-dichloropurine (V) by means of triethylamine in DMF yields 2,6-dichloro-9-(2-benzoyloxyethoxymethyl)purine (VI),which is aminated and debenzoylated by treatment with NH3 in methanol at 95 C in a pressure vessel giving 2-chloro-9-(2-hydroxyethoxymethyl)adenine (VII).The Sandmeyer reaction of (VII) with NaNO2 in acetic acid affords 2-chloro-9-(2-hydroxyethoxymethyl)hypoxanthine (VIII),which is finally amonolyzed with ammonia in methanol at 125 C in a pressure vessel.

合成路线:The condensation of guanine (IX) with refluxing hexamethyldisilazane followed by reaction with 1-benzoyloxy-2-chloromethoxyethane (IV) by means of triethylamine in refluxing benzene gives 9-(2-benzoyloxyethoxymethyl)guanine (X),which is finally hydrolyzed with ammonia in methanol at 80 C in a pressure vessel.

参考文献标题:Acycloguanosine
文献作者:Castar,J.; Hillier,K.
参考来源:Drugs Fut 1978,3(11),788


合成路线:The reaction of benzonitrile (I) with refluxing ethylene glycol (II) gives ethylene glycol monobenzoate (III),which is chloromethylated with formaldehyde and dry HCl in CH2Cl2 affording 1-benzoyloxy-2-chloromethoxyethane (IV).The condensation of (IV) with 2,6-dichloropurine (V) by means of triethylamine in DMF yields 2,6-dichloro-9-(2-benzoyloxyethoxymethyl)purine (VI),which is aminated and debenzoylated by treatment with NH3 in methanol at 95 C in a pressure vessel giving 2-chloro-9-(2-hydroxyethoxymethyl)adenine (VII).The Sandmeyer reaction of (VII) with NaNO2 in acetic acid affords 2-chloro-9-(2-hydroxyethoxymethyl)hypoxanthine (VIII),which is finally amonolyzed with ammonia in methanol at 125 C in a pressure vessel.
参考文献标题:9-(2-Hydroxyethoxy)guanine activity aganist viruses of the herpes group
文献作者:Schaeffer,H.J.; et al.
参考来源:Nature 1978,272583-585


产品链接: CAS No. 59277-89-3››