合成路线:The synthesis of penciclovir by two related ways has been reported:1) The reaction of 2-(hydroxymethyl)butane-1,4-diol (I) with formaldehyde (or an aldehyde such as trimethylacetaldehyde) (II) by means of H2SO4 (or p-toluenesulfonic acid,TsOH) gives the dioxane (III),which by reaction first with methanesulfonyl chloride and triethylamine and then with NaI in acetone affords the corresponding 5-(2-iodoethyl)-1,3-dioxane (IV).The reaction of (IV) with 2-amino-6-chloropurine (V) by means of K2CO3 in DMF gives the corresponding condensation product (VI),which is finally hydrolyzed and deprotected with refluxing 2M aqueous HCl.2) The reaction of triol (I) with 2,2-dimethoxypropane (VII) by means of TsOH gives the corresponding 1,3-dioxane (VIII),which by reaction with triphenylphosphine and CBr4 is converted to the 5-(2-bromoethyl) derivative (IX).The reaction of (IX) with the purine (V) by means of K2CO3 as before affords the corresponding condensation product (X),which is hydrolyzed and deprotected with 2M HCl as before.
参考文献标题:Influence of remote structure upon regioselectivity in the N-alkylation of 2-amino-6-chloropurine: Application to the synthesis of penciclovir
文献作者:Grinter,T.J.; Choudary,B.M.; MacBeath,F.S.; Parratt,M.J.; Geen,G.R.
参考来源:Nucleosides Nucleotides 1994,13(4),979
合成路线:This compound has been obtained by two similar ways:1) The reaction of 6-chloropurine-2-amine (I) with 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (II) by means of K2CO3 in DMF gives the expected condensation product (III),which is methanolized with HCl/methanol yielding 2-[2-(2-amino-6-methoxypurin-9-yl)ethyl]malonic acid dimethyl ester (IV).The reduction of (IV) with NaBH4 in tert-butanol/methanol affords the corresponding diol (V),which is finally converted into pecnciclovir by hydrolysis with 2N NaOH.2) The reaction of purine (I) with 3-bromopropane-1,1,1-tricarboxylic acid triethyl ester (VI) by means ofK2CO3 in DMF gives the expected condensation product (VII),which is partially decarboxylated with sodium methoxide in methanol yielding 2-[2-(2-amino-6-chloropurin-9-yl)ethyl]malonic acid diethyl ester (VIII).The reduction of (VIII) with NaBH4 in tert-butanol/methanol followed by acetylation with acetic anhydride affords the corresponding diol diacetate (IX),which is finally converted into penciclovir by hydrlysis with 2N HCl.
合成路线:A synthesis of famciclovir that corresponds to that previously published and studies on its oral bioavailability in rats and mice,identifying famciclovir as the preferred prodrug of BRL-39123 (penciclovir),have been published.
合成路线:The reaction of purine (I) with 3-bromopropane-1,1,1-tricarboxylic acid triethyl ester (II) by means ofK2CO3 in DMF gives the expected condensation product (III),which is partially decarboxylated with sodium methoxide in methanol yielding 2-[2-(2-amino-6-chloropurin-9-yl)ethyl]malonic acid diethyl ester (IV).The reduction of (IV) with NaBH4 in tert-butanol/methanol followed by acetylation with acetic anhydride affords the corresponding diol diacetate (V),which is finally converted into famciclovir by reductive dechlorination with H2 over Pd/C in ethyl acetate/triethylamine.
参考文献标题:A direct approach to the synthesis of famciclovir and penciclovir
文献作者:Choudary,B.M.; Geen,G.R.; Kincey,P.M.; Parratt,M.J.; Dales,J.R.M.; Johnson,G.P.; O'Donnell,S.; Tudor,D.W.; Woods,N.
参考来源:Nucleosides Nucleotides 1996,15(5),981
合成路线:This compound has been obtained by two similar ways:1) The reaction of 6-chloropurine-2-amine (I) with 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (II) by means of K2CO3 in DMF gives the expected condensation product (III),which is methanolized with HCl/methanol yielding 2-[2-(2-amino-6-methoxypurin-9-yl)ethyl]malonic acid dimethyl ester (IV).The reduction of (IV) with NaBH4 in tert-butanol/methanol affords the corresponding diol (V),which is finally converted into pecnciclovir by hydrolysis with 2N NaOH.2) The reaction of purine (I) with 3-bromopropane-1,1,1-tricarboxylic acid triethyl ester (VI) by means ofK2CO3 in DMF gives the expected condensation product (VII),which is partially decarboxylated with sodium methoxide in methanol yielding 2-[2-(2-amino-6-chloropurin-9-yl)ethyl]malonic acid diethyl ester (VIII).The reduction of (VIII) with NaBH4 in tert-butanol/methanol followed by acetylation with acetic anhydride affords the corresponding diol diacetate (IX),which is finally converted into penciclovir by hydrlysis with 2N HCl.
参考文献标题:A new class of nucleoside analogues.Synthesis of N1-pyrimidinyl- and N9-purinyl-4'-hydroxy-3'-(hydroxymethyl)butanes
文献作者:Grose,W.F.A.; Pandit,U.K.; Eggelte,T.A.
参考来源:Synth Commun 1972,2345-351
合成路线:This compound has been obtained by two similar ways:1) The reaction of 6-chloropurine-2-amine (I) with 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (II) by means of K2CO3 in DMF gives the expected condensation product (III),which is methanolized with HCl/methanol yielding 2-[2-(2-amino-6-methoxypurin-9-yl)ethyl]malonic acid dimethyl ester (IV).The reduction of (IV) with NaBH4 in tert-butanol/methanol affords the corresponding diol (V),which is finally converted into pecnciclovir by hydrolysis with 2N NaOH.2) The reaction of purine (I) with 3-bromopropane-1,1,1-tricarboxylic acid triethyl ester (VI) by means ofK2CO3 in DMF gives the expected condensation product (VII),which is partially decarboxylated with sodium methoxide in methanol yielding 2-[2-(2-amino-6-chloropurin-9-yl)ethyl]malonic acid diethyl ester (VIII).The reduction of (VIII) with NaBH4 in tert-butanol/methanol followed by acetylation with acetic anhydride affords the corresponding diol diacetate (IX),which is finally converted into penciclovir by hydrlysis with 2N HCl.
参考文献标题:An improved synthesis of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine
文献作者:Jarvest,R.L.; Harnden,M.R.
参考来源:Tetrahedron Lett 1985,264265-68
合成路线:This compound has been obtained by two similar ways:1) The reaction of 6-chloropurine-2-amine (I) with 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (II) by means of K2CO3 in DMF gives the expected condensation product (III),which is methanolized with HCl/methanol yielding 2-[2-(2-amino-6-methoxypurin-9-yl)ethyl]malonic acid dimethyl ester (IV).The reduction of (IV) with NaBH4 in tert-butanol/methanol affords the corresponding diol (V),which is finally converted into pecnciclovir by hydrolysis with 2N NaOH.2) The reaction of purine (I) with 3-bromopropane-1,1,1-tricarboxylic acid triethyl ester (VI) by means ofK2CO3 in DMF gives the expected condensation product (VII),which is partially decarboxylated with sodium methoxide in methanol yielding 2-[2-(2-amino-6-chloropurin-9-yl)ethyl]malonic acid diethyl ester (VIII).The reduction of (VIII) with NaBH4 in tert-butanol/methanol followed by acetylation with acetic anhydride affords the corresponding diol diacetate (IX),which is finally converted into penciclovir by hydrlysis with 2N HCl.
参考文献标题:Synthesis and antiviral activity of 9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]purines
文献作者:Boyd,M.R.; Jarvest,R.L.; Bacon,T.H.; Harnden,M.R.
参考来源:J Med Chem 1987,301636-42
合成路线:This compound has been obtained by two similar ways:1) The reaction of 6-chloropurine-2-amine (I) with 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (II) by means of K2CO3 in DMF gives the expected condensation product (III),which is methanolized with HCl/methanol yielding 2-[2-(2-amino-6-methoxypurin-9-yl)ethyl]malonic acid dimethyl ester (IV).The reduction of (IV) with NaBH4 in tert-butanol/methanol affords the corresponding diol (V),which is finally converted into pecnciclovir by hydrolysis with 2N NaOH.2) The reaction of purine (I) with 3-bromopropane-1,1,1-tricarboxylic acid triethyl ester (VI) by means ofK2CO3 in DMF gives the expected condensation product (VII),which is partially decarboxylated with sodium methoxide in methanol yielding 2-[2-(2-amino-6-chloropurin-9-yl)ethyl]malonic acid diethyl ester (VIII).The reduction of (VIII) with NaBH4 in tert-butanol/methanol followed by acetylation with acetic anhydride affords the corresponding diol diacetate (IX),which is finally converted into penciclovir by hydrlysis with 2N HCl.
参考文献标题:Development of 9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]purines as potential therapeutic agents for treatment of human herpesvirus infections
文献作者:Hardern,D.N.
参考来源:Drugs Fut 1989,14(4),347
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