合成路线:The reaction of epichlorohydrin (I) with benzyl alcohol (II) by means of NaOH in water gives 1,3-di-O-benzylglycerol (III),which is condensed with paraformaldehyde by means of HCl in methylene chloride to yield 1,3-di-O-benzyl-2-O-(chloromethyl)glycerol (IV).Acetylation of (IV) with potassium acetate in acetone affords 1,3-di-O-benzyl-2-O-(acetoxymethyl)glycerol (V),which is condensed with diacetylguanine (VI) by means of p-toluenesulfonic acid in sulfolane giving N2-acetyl-9-[[1,3-bis(benzyloxy)-2-propoxy]methyl]guanine (VII).Finally,this compound is deprotected by a treatment with palladium hydroxide in refluxing cyclohexane.
参考文献标题:9-(1,3-Dihydroxy-2-propoxymethyl)guanine as antiviral agent
文献作者:Verheyden,J.P.; Martin,J.C.(Roche Bioscience)
参考来源:EP 0066208; JP 4217983; JP 57203086; US 4355032
合成路线:The reaction of epichlorohydrin (I) with benzyl alcohol (II) by means of NaOH in water gives 1,3-di-O-benzylglycerol (III),which is condensed with paraformaldehyde by means of HCl in methylene chloride to yield 1,3-di-O-benzyl-2-O-(chloromethyl)glycerol (IV).Acetylation of (IV) with potassium acetate in acetone affords 1,3-di-O-benzyl-2-O-(acetoxymethyl)glycerol (V),which is condensed with diacetylguanine (VI) by means of p-toluenesulfonic acid in sulfolane giving N2-acetyl-9-[[1,3-bis(benzyloxy)-2-propoxy]methyl]guanine (VII).Finally,this compound is deprotected by a treatment with palladium hydroxide in refluxing cyclohexane.
合成路线:The condensation of N2-acetylguanine (VIII) with (V) by means of ammonium sulfate in refluxing HMDS gives (VII).This compound is deprotected by a treatment with palladium hydroxide in refluxing cyclohexane.
合成路线:The condensation of 6-chloroguanine (IX) with (V) by means of ammonium sulfate in refluxing HMDS gives 9-[[1,3-bis(benzyloxy)-2-propoxy]methyl]-6-chloroguanine (XI),which is treated with sodium methoxide and mercaptoethanol in refluxing methanol to yield 9-[[1,3-bisbenzyloxy)-2-propoxy]methyl]guanine (XI),which is finally deprotected by a treatment with palladium hydroxide in refluxing cyclohexane.
合成路线:The acetylation of 4-hydroxymethyl-1,3-dioxolane (XII) gives the corresponding acetate (XIII),which by reaction with acetic anhydride and ZnCl2 is converted to 1,3-diacetoxy-2-(acetoxymethoxy)propane (XIV).The condensation of (XIV) with diacetylguanine (VI) by means of ethanesulfonic acid (B) yields the triacetoxy precursor (XV),which is hydrolyzed with aqueous methylamine.
参考文献标题:BIOLF-62
文献作者:Pento,J.T.; Serradell,M.N.; Castar,J.
参考来源:Drugs Fut 1985,10(5),365
合成路线:The condensation of diacetyl guanine (I) with 1,3-diacetoxy-2-(acetoxymethoxy)propane (II) by means of TsOH in hot DMF gives the target intermediate,N2-acetyl-9-[2-acetoxy-1-(acetoxymethyl)ethoxymethyl]guanine (III).(see Synthline Scheme no.11147104a,intermediate no.(XV)).
参考文献标题:A process for the preparation of ganciclovir intermediate N2-acetyl-9-(1,3-diacetoxy-2-propoxymethyl)guanine
文献作者:Kumar,Y.; Khanduri,C.H.; Ray,P.C.; Babu,J.S.(Ranbaxy Laboratories Ltd.)
参考来源:WO 0333498
合成路线:The condensation of diacetyl guanine (I) with 1,3-diacetoxy-2-(acetoxymethoxy)propane (II) by means of TsOH in hot DMF gives the target intermediate,N2-acetyl-9-[2-acetoxy-1-(acetoxymethyl)ethoxymethyl]guanine (III).(see Synthline Scheme no.11147104a,intermediate no.(XV)).
参考文献标题:Process for the synthesis of ganciclovir
文献作者:Kumar,Y.; Khanduri,C.H.; Ray,P.C.; Babu,J.S.(Ranbaxy Laboratories Ltd.)
参考来源:WO 0448380
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 epichlorohydrin (I) with benzyl alcohol (II) by means of NaOH in water gives 1,3-di-O-benzylglycerol (III),which is condensed with paraformaldehyde by means of HCl in methylene chloride to yield 1,3-di-O-benzyl-2-O-(chloromethyl)glycerol (IV).Acetylation of (IV) with potassium acetate in acetone affords 1,3-di-O-benzyl-2-O-(acetoxymethyl)glycerol (V),which is condensed with diacetylguanine (VI) by means of p-toluenesulfonic acid in sulfolane giving N2-acetyl-9-[[1,3-bis(benzyloxy)-2-propoxy]methyl]guanine (VII).Finally,this compound is deprotected by a treatment with palladium hydroxide in refluxing cyclohexane.
合成路线:The condensation of N2-acetylguanine (VIII) with (V) by means of ammonium sulfate in refluxing HMDS gives (VII).This compound is deprotected by a treatment with palladium hydroxide in refluxing cyclohexane.
合成路线:The condensation of 6-chloroguanine (IX) with (V) by means of ammonium sulfate in refluxing HMDS gives 9-[[1,3-bis(benzyloxy)-2-propoxy]methyl]-6-chloroguanine (XI),which is treated with sodium methoxide and mercaptoethanol in refluxing methanol to yield 9-[[1,3-bisbenzyloxy)-2-propoxy]methyl]guanine (XI),which is finally deprotected by a treatment with palladium hydroxide in refluxing cyclohexane.
合成路线:The acetylation of 4-hydroxymethyl-1,3-dioxolane (XII) gives the corresponding acetate (XIII),which by reaction with acetic anhydride and ZnCl2 is converted to 1,3-diacetoxy-2-(acetoxymethoxy)propane (XIV).The condensation of (XIV) with diacetylguanine (VI) by means of ethanesulfonic acid (B) yields the triacetoxy precursor (XV),which is hydrolyzed with aqueous methylamine.
参考文献标题:A new nucleoside analog,9-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl]guanine,highly active in vitro aganist herpes simplex virus types 1 and 2
文献作者:Smith,K.O.; Galloway,K.S.; Kennell,W.L.; Ogilvie,K.K.; Radatus,B.K.
参考来源:Antimicrob Agents Chemother 1982,22(1),55-61
产品链接: CAS No. 82410-32-0›› 产品链接: CAS No.107910-75-8››